9,164 results match your criteria Molecular biology of the cell[Journal]


Isoform-specific Ras signaling is growth factor dependent.

Mol Biol Cell 2019 Feb 20:mbcE18100676. Epub 2019 Feb 20.

Division of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, L69 3BX, UK.

HRAS, NRAS and KRAS isoforms are almost identical proteins that are ubiquitously expressed and activate a common set of effectors. In vivo studies have revealed that they are not biologically redundant; however, the isoform-specificity of Ras signaling remains poorly understood. Using a novel panel of isogenic SW48 cell lines endogenously expressing wild type or G12V mutated activated Ras isoforms we have performed a detailed characterization of endogenous isoform-specific mutant Ras signaling. Read More

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http://dx.doi.org/10.1091/mbc.E18-10-0676DOI Listing
February 2019

The relationship between metastatic potential and in vitro mechanical properties of osteosarcoma cells.

Mol Biol Cell 2019 Feb 20:mbcE18080545. Epub 2019 Feb 20.

Biomechanics Laboratory, University Hospital Balgrist, University of Zürich, 8008 Zürich, Switzerland.

Osteosarcoma is the most frequent primary tumor of bone and is characterized by its high tendency to metastasize in lungs. Although in case of being early diagnosed treatment results in a 5-year survival rate of nearly 60%, prognosis of patients with secondary lesions at diagnosis is poor and their 5-year survival rate remains below 30%. In the present work we have used a number of analytical methods to investigate the impact of increased metastatic potential on the biophysical properties and force generation of osteosarcoma cells. Read More

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http://dx.doi.org/10.1091/mbc.E18-08-0545DOI Listing
February 2019

Choice between 1- and 2-furrow cytokinesis in Caenorhabditis elegans embryos with tripolar spindles.

Mol Biol Cell 2019 Feb 20:mbcE19010075. Epub 2019 Feb 20.

Cell Architecture Laboratory, Department of Chromosome Science, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.

Excessive centrosomes often lead to multipolar spindles, and thus probably to multipolar mitosis and aneuploidy. In Caenorhabditis elegans, approximately 70% of the paternal emb-27 mutant embryonic cells contained more than two centrosomes and formed multipolar spindles. However, only 30% of the cells with tripolar spindles formed two cytokinetic furrows. Read More

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http://dx.doi.org/10.1091/mbc.E19-01-0075DOI Listing
February 2019

Myosin IIA drives membrane bleb retraction.

Mol Biol Cell 2019 Feb 20:mbcE18110752. Epub 2019 Feb 20.

Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Membrane blebs are specialized cellular protrusions that play diverse roles in processes such as cell division and cell migration. Blebbing can be divided into three distinct phases- bleb nucleation, bleb growth and bleb retraction. Following nucleation and bleb growth, the actin cortex, comprising actin, cross-linking proteins and non-muscle myosin II (MII), begins to re-assemble on the membrane. Read More

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http://dx.doi.org/10.1091/mbc.E18-11-0752DOI Listing
February 2019

Cellular Crowding Influences Extrusion and Proliferation to Facilitate Epithelial Tissue Repair.

Mol Biol Cell 2019 02 20:mbcE18050295. Epub 2019 Feb 20.

Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030.

Epithelial wound healing requires a complex orchestration of cellular rearrangements and movements to restore tissue architecture and function after injury. While it is well-known that mechanical forces can affect tissue morphogenesis and patterning, how the biophysical cues generated after injury influence cellular behaviors during tissue repair is not well understood. Using time-lapse confocal imaging of epithelial tissues in living zebrafish larvae, we provide evidence that localized increases in cellular crowding during wound closure promote the extrusion of non-apoptotic cells via mechanically regulated stretch-activated ion channels (SACs). Read More

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http://dx.doi.org/10.1091/mbc.E18-05-0295DOI Listing
February 2019

The putative G protein-coupled receptor GrlD mediates extracellular polyphosphate sensing in Dictyostelium discoideum.

Mol Biol Cell 2019 Feb 20:mbcE18100686. Epub 2019 Feb 20.

Department of Biology, Texas A&M University, College Station, TX 77843-3474 USA.

Five or more orthophosphates bound together by high energy phospho-anhydride bonds are highly ubiquitous inorganic molecules called polyphosphate. Polyphosphate acts as a signaling molecule eliciting a number of responses in eukaryotic cells, but the mechanisms mediating these effects are poorly understood. Proliferating Dictyostelium discoideum cells accumulate extracellular polyphosphate. Read More

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http://dx.doi.org/10.1091/mbc.E18-10-0686DOI Listing
February 2019

Mps1 regulates spindle morphology through MCRS1 to promote chromosome alignment.

Mol Biol Cell 2019 Feb 20:mbcE18090546. Epub 2019 Feb 20.

Arts and Science, New York University at Shanghai, Shanghai, 200122, China.

Accurate partitioning of chromosomes during mitosis is essential for genetic stability and requires the assembly of the dynamic mitotic spindle and proper kinetochore-microtubule attachment. The spindle assembly checkpoint (SAC) monitors the incompleteness and errors in kinetochore-microtubule attachment and delays anaphase. The SAC kinase Mps1 regulates the recruitment of downstream effectors to unattached kinetochores. Read More

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February 2019
1 Read

The P5A ATPase Spf1p is stimulated by phosphatidylinositol 4-phosphate and influences cellular sterol homeostasis.

Mol Biol Cell 2019 Feb 20:mbcE18060365. Epub 2019 Feb 20.

Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg C, Denmark.

P5A ATPases are expressed in the endoplasmic reticulum (ER) of all eukaryotic cells, and their disruption results in severe ER stress. However, the function of these ubiquitous membrane proteins, which belong to the P-type ATPase superfamily, is unknown. We purified a functional tagged version of the Saccharomyces cerevisiae P5A ATPase Spf1p and observed that the ATP hydrolytic activity of the protein is stimulated by phosphatidylinositol 4-phosphate (PI4P). Read More

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http://dx.doi.org/10.1091/mbc.E18-06-0365DOI Listing
February 2019

Correction.

Authors:

Mol Biol Cell 2019 Feb;30(4):524

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http://dx.doi.org/10.1091/mbc.E17-12-0726-corrDOI Listing
February 2019

Single particle tracking localization microscopy reveals nonaxonemal dynamics of intraflagellar transport proteins at the base of mammalian primary cilia.

Mol Biol Cell 2019 Feb 13:mbcE18100654. Epub 2019 Feb 13.

Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 10617, Taiwan.

Primary cilia play a vital role in cellular sensing and signaling. An essential component of ciliogenesis is intraflagellar transport (IFT) involving in IFT-protein recruitment, axonemal engagement of IFT-protein complexes, etc. The mechanistic understanding of these processes at the ciliary base was largely missing, because it is challenging to observe the motion of IFT proteins in this crowded region using conventional microscopy. Read More

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http://dx.doi.org/10.1091/mbc.E18-10-0654DOI Listing
February 2019

Mechanosensitive Rap1 activation promotes barrier function of lung vascular endothelium under cyclic stretch.

Mol Biol Cell 2019 Feb 13:mbcE18070422. Epub 2019 Feb 13.

Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201.

Mechanical ventilation remains an imperative treatment for the patients with acute respiratory distress syndrome, but can also exacerbate lung injury. We have previously described a key role of RhoA GTPase in high cyclic stretch (CS)-induced endothelial (EC) barrier dysfunction. However, cellular mechanotransduction complexes remain to be characterized. Read More

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https://www.molbiolcell.org/doi/10.1091/mbc.E18-07-0422
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http://dx.doi.org/10.1091/mbc.E18-07-0422DOI Listing
February 2019
2 Reads

Actin turnover ensures uniform tension distribution during cytokinetic actomyosin ring contraction.

Mol Biol Cell 2019 Feb 13:mbcE18080511. Epub 2019 Feb 13.

Centre for Mechanochemical Cell Biology and Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, CV4 7AL UK.

In many eukaryotes cytokinesis is facilitated by the contraction of an actomyosin ring (AMR). The exact mechanisms that lead to this contractility are unknown, although some models posit that actin turnover in the AMR is essential. The effect of reduced actin dynamics during AMR formation has been well studied in Schizosaccharomyces pombe; however the corresponding effects on AMR contraction are not well understood. Read More

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http://dx.doi.org/10.1091/mbc.E18-08-0511DOI Listing
February 2019

MAPK modulation of yeast pheromone signaling output and the role of phosphorylation sites in the scaffold protein Ste5.

Mol Biol Cell 2019 Feb 6:mbcE18120793. Epub 2019 Feb 6.

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605.

Mitogen-activated protein kinases (MAPKs) mediate numerous eukaryotic signaling responses. They also can modulate their own signaling output, via positive or negative feedback loops. In the yeast pheromone response pathway, the MAPK Fus3 triggers negative feedback that dampens its own activity. Read More

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http://dx.doi.org/10.1091/mbc.E18-12-0793DOI Listing
February 2019

Yeast-to-hypha transition of Schizosaccharomyces japonicus in response to environmental stimuli.

Mol Biol Cell 2019 02 6:mbcE18120774. Epub 2019 Feb 6.

Department of fundamental microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore building, CH-1015 Lausanne, Switzerland.

Many fungal species are dimorphic, exhibiting both unicellular yeast-like and filamentous forms. Schizosaccharomyces japonicus, a member of the fission yeast clade, is one such dimorphic fungus. Here, we first identify fruit extracts as natural, stress-free, starvation-independent inducers of filamentation, which we use to describe the properties of the dimorphic switch. Read More

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http://dx.doi.org/10.1091/mbc.E18-12-0774DOI Listing
February 2019

Cellular eIF2B subunit localisation: implications for the integrated stress response and its control by small molecule drugs.

Mol Biol Cell 2019 Feb 6:mbcE18080538. Epub 2019 Feb 6.

Biomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield, S1 1WB.

eIF2 is a G protein critical for translation. It is tightly regulated in the integrated stress response (ISR) via phosphorylation of eIF2α and the subsequent control of eIF2B, a multisubunit guanine nucleotide exchange factor (GEF). Through studying the localisation of eIF2B subunits we identified cytoplasmic eIF2B bodies in mammalian cells. Read More

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http://dx.doi.org/10.1091/mbc.E18-08-0538DOI Listing
February 2019

Fascetto (PRC1) interacting protein (FIP) ensures proper cytokinesis and ploidy.

Mol Biol Cell 2019 Feb 6:mbcE18090573. Epub 2019 Feb 6.

Cell and Developmental Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda MD 20892.

Cell division is critical for development, organ growth, and tissue repair. The later stages of cell division include the formation of the microtubule (MT)-rich central spindle in anaphase, which is required to properly define the cell equator, guide the assembly of the acto-myosin contractile ring, and ultimately ensure complete separation and isolation of the two daughter cells via abscission. Much is known about the molecular machinery that forms the central spindle, including proteins needed to generate the antiparallel overlapping interzonal MTs. Read More

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https://www.molbiolcell.org/doi/10.1091/mbc.E18-09-0573
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http://dx.doi.org/10.1091/mbc.E18-09-0573DOI Listing
February 2019
3 Reads

Action of Arl1 GTPase and golgin Imh1 in Ypt6-independent retrograde transport from endosomes to the trans-Golgi network.

Mol Biol Cell 2019 Feb 6:mbcE18090579. Epub 2019 Feb 6.

Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.

The Arf and Rab/Ypt GTPases coordinately regulate membrane traffic and organelle structure by regulating vesicle formation and fusion. Ample evidence has indicated that proteins in these two families may function in parallel or complementarily; however, the manner in which Arf and Rab/Ypt proteins perform interchangeable function remains unclear. In this study, we report that a Golgi-localized Arf, Arl1, could suppress the Ypt6 dysfunction via its effector golgin, Imh1, but not via the lipid flippase Drs2. Read More

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http://dx.doi.org/10.1091/mbc.E18-09-0579DOI Listing
February 2019
1 Read

The RhoGAP SPV-1 regulates calcium signaling to control the contractility of the C. elegans spermatheca during embryo transits.

Mol Biol Cell 2019 Feb 6:mbcE18100633. Epub 2019 Feb 6.

Department of Biology, Northeastern University, Boston, MA.

Contractility of the non-muscle and smooth muscle cells that comprise biological tubing is regulated by the Rho-ROCK and calcium signaling pathways. Although many molecular details about these signaling pathways are known, less is known about how they are coordinated spatiotemporally in biological tubes. The spermatheca of the C. Read More

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http://dx.doi.org/10.1091/mbc.E18-10-0633DOI Listing
February 2019

Cell cycle dependent association of polo kinase Cdc5 with CENP-A contributes to faithful chromosome segregation in budding yeast.

Mol Biol Cell 2019 Feb 6:mbcE18090584. Epub 2019 Feb 6.

Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Evolutionarily conserved polo-like kinase, Cdc5 (Plk1 in humans) associates with kinetochores during mitosis, however, the role of cell cycle dependent centromeric ( CEN) association of Cdc5 and its substrates that exclusively localize to the kinetochore have not been characterized. Here we report that evolutionarily conserved CEN histone H3 variant, Cse4 (CENP-A in humans) is a substrate of Cdc5, and that the cell cycle regulated association of Cse4 with Cdc5 is required for cell growth. Cdc5 contributes to Cse4 phosphorylation in vivo and interacts with Cse4 in mitotic cells. Read More

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http://dx.doi.org/10.1091/mbc.E18-09-0584DOI Listing
February 2019
1 Read

PRMT7 Methylates Eukaryotic Translation Initiation Factor 2α and Regulates its Role in Stress Granule Formation.

Mol Biol Cell 2019 Jan 30:mbcE18050330. Epub 2019 Jan 30.

Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada, K1H 8M5.

Protein arginine methyltransferases (PRMTs) are a family of enzymes that modify proteins by methylating the guanidino nitrogen atoms of arginine residues to regulate cellular processes such as chromatin remodelling, pre-mRNA splicing, and signal transduction. PRMT7 is the single type III PRMT solely capable of arginine monomethylation. To date, other than histone proteins, there are very few identified substrates of PRMT7. Read More

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http://dx.doi.org/10.1091/mbc.E18-05-0330DOI Listing
January 2019
4.466 Impact Factor

The adaptor protein melanophilin regulates dynamic myosin-Va:cargo interaction and dendrite development in melanocytes.

Mol Biol Cell 2019 Jan 30:mbcE18040237. Epub 2019 Jan 30.

School of Life Sciences, University of Nottingham, Nottingham, NG7 2UH, UK.

Regulation of organelle transport by the cytoskeleton is fundamental for eukaryotic survival. Cytoskeleton motors are typically modular proteins with conserved motor and diverse cargo binding domains. Motor:cargo interactions are often indirect and mediated by adaptor proteins e. Read More

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http://dx.doi.org/10.1091/mbc.E18-04-0237DOI Listing
January 2019

A method to quantify centrosomes at single-cell level in human normal and cancer tissue.

Mol Biol Cell 2019 Jan 30:mbcE18100651. Epub 2019 Jan 30.

Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ 85724, USA.

Centrosome abnormalities are emerging hallmarks of cancer. The over-production of centrosomes (known as centrosome amplification) has been reported in a variety of cancers and is currently being explored as a promising target for therapy. However, to understand different types of centrosome abnormalities and their impact on centrosome function during tumor progression, as well as identify tumor subtypes that would respond to targeting a centrosome abnormality, a reliable method to accurately quantify centrosomes in human tissue samples is needed. Read More

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https://www.molbiolcell.org/doi/10.1091/mbc.E18-10-0651
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January 2019
3 Reads

A unified model for microtubule rescue.

Mol Biol Cell 2019 Jan 23:mbcE18080541. Epub 2019 Jan 23.

Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO.

How microtubules transition from depolymerization to polymerization, known as rescue, is poorly understood. Here we examine two models for rescue: 1) an 'end-driven' model in which the depolymerizing end stochastically switches to a stable state; and 2) a 'lattice-driven' model in which rescue-sites are integrated into the microtubule prior to depolymerization. We test these models using a combination of computational simulations and in vitro experiments with purified tubulin. Read More

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http://dx.doi.org/10.1091/mbc.E18-08-0541DOI Listing
January 2019
1 Read

Adapter protein Ste50p directly modulates yeast MAPK signaling specificity through differential connections of its RA domain.

Mol Biol Cell 2019 Jan 16:mbcE18110708. Epub 2019 Jan 16.

Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC, Canada H4A 3J1.

Discriminating among diverse environmental stimuli is critical for organisms to ensure their proper development, homeostasis and survival. Saccharomyces cerevisiae regulates mating, osmoregulation and filamentous growth using three different MAPK signaling pathways that share common components and therefore must ensure specificity. The adapter protein, Ste50p activates Ste11p, the MAP3K of all three modules. Read More

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https://www.molbiolcell.org/doi/10.1091/mbc.E18-11-0708
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http://dx.doi.org/10.1091/mbc.E18-11-0708DOI Listing
January 2019
4 Reads

A computational model of the early stages of acentriolar meiotic spindle assembly.

Mol Biol Cell 2019 Jan 16:mbcE18100644. Epub 2019 Jan 16.

CIRB, Collège de France, UMR7241/U1050, Paris F-75005, France.

The mitotic spindle is an ensemble of microtubules responsible for the repartition of the chromosomal content between the two daughter cells during division. In metazoans, spindle assembly is a gradual process involving dynamic microtubules and recruitment of numerous associated proteins and motors. During mitosis, centrosomes organize and nucleate the majority of spindle microtubules. Read More

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https://www.molbiolcell.org/doi/10.1091/mbc.E18-10-0644
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http://dx.doi.org/10.1091/mbc.E18-10-0644DOI Listing
January 2019
4 Reads

Tristetraprolin-mediated hexokinase 2 expression regulation contributes glycolysis in cancer cells.

Mol Biol Cell 2019 Jan 16:mbcE18090606. Epub 2019 Jan 16.

Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.

Hexokinase 2 (HK2) catalyzes the first step of glycolysis and is upregulated in cancer cells. The mechanism by which HK2 expression is upregulated in cancer cells has not been fully elucidated. Tristetraprolin (TTP) is an AU-rich element (ARE)-binding protein that inhibits the expression of ARE-containing genes by enhancing mRNA degradation. Read More

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http://dx.doi.org/10.1091/mbc.E18-09-0606DOI Listing
January 2019

Tropomyosin Isoforms differentially tune actin filament length and disassembly.

Mol Biol Cell 2019 Jan 16:mbcE18120815. Epub 2019 Jan 16.

Department of Biology, Rosenstiel Basic Medical Science Research Center, Brandeis University, 415 South St., Waltham, MA, 02454, USA.

Cellular actin networks exhibit diverse filamentous architectures and turnover dynamics, but how these differences are specified remains poorly understood. Here, we used multicolor TIRF microscopy to ask how decoration of actin filaments by five biologically-prominent Tropomyosin (TPM) isoforms influences disassembly induced by Cofilin alone, or by the collaborative effects of Cofilin, Coronin, and AIP1 (CCA). TPM decoration restricted Cofilin binding to pointed ends, while not interfering with Coronin binding to filament sides. Read More

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http://dx.doi.org/10.1091/mbc.E18-12-0815DOI Listing
January 2019

Uncoupling of transcriptomic and cytological differentiation in mouse spermatocytes with impaired meiosis.

Mol Biol Cell 2019 Jan 16:mbcE18100681. Epub 2019 Jan 16.

The Jackson Laboratory, Bar Harbor, Maine 04609 USA.

Cell differentiation is driven by changes in gene expression that manifest as changes in cellular phenotype or function. Altered cellular phenotypes, stemming from genetic mutations or other perturbations, are widely assumed to directly correspond to changes in the transcriptome and vice versa. Here, we exploited the cytologically well-defined Prdm9 mutant mouse as a model of developmental arrest to test whether parallel programs of cellular differentiation and gene expression are tightly coordinated, or can be disassociated. Read More

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http://dx.doi.org/10.1091/mbc.E18-10-0681DOI Listing
January 2019

Interactions of the dynein-2 intermediate chain WDR34 with the light chains are required for ciliary retrograde protein trafficking.

Mol Biol Cell 2019 Jan 16:mbcE18100678. Epub 2019 Jan 16.

Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.

The dynein-2 complex drives retrograde ciliary protein trafficking by associating with the intraflagellar transport (IFT) machinery, containing IFT-A and IFT-B complexes. We recently showed that the dynein-2 complex, which comprises 11 subunits, can be divided into three subcomplexes; DYNC2H1-DYNC2LI1, WDR34-DYNLL1/DYNLL2-DYNLRB1/DYNLRB2, and WDR60-TCTEX1D2-DYNLT1/DYNLT3. In this study, we demonstrated that the WDR34 intermediate chain interacts with the two light chains, DYNLL1/DYNLL2 and DYNLRB1/DYNLRB2, via its distinct sites. Read More

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http://dx.doi.org/10.1091/mbc.E18-10-0678DOI Listing
January 2019

Dual binding motifs underpin the hierarchical association of perilipins1-3 with lipid droplets.

Mol Biol Cell 2019 Jan 16:mbcE18080534. Epub 2019 Jan 16.

Laboratoire de Physique Statistique, Ecole Normale Supérieure, PSL Research University, Sorbonne Université, UPMC Université Paris 06, Université Paris Diderot, CNRS, Paris, France.

Lipid droplets (LDs) in all eukaryotic cells are coated with at least one of the perilipin family of proteins. They all regulate key intracellular lipases but do so to significantly different extents. Where more than one perilipin is expressed in a cell, they associate with LDs in a hierarchical manner. Read More

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http://dx.doi.org/10.1091/mbc.E18-08-0534DOI Listing
January 2019

A conserved mechanism for mitochondria-dependent dynein anchoring.

Mol Biol Cell 2019 Jan 16:mbcE18070466. Epub 2019 Jan 16.

Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.

Mitochondrial anchors have functions that extend beyond simply positioning mitochondria. In budding yeast, mitochondria drive the assembly of the mitochondrial anchor protein Num1 into clusters, which serve to anchor mitochondria as well as dynein to the cell cortex. Here, we explore a conserved role for mitochondria in dynein anchoring by examining the tethering functions of the evolutionarily distant S. Read More

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http://dx.doi.org/10.1091/mbc.E18-07-0466DOI Listing
January 2019

GRASP depletion-mediated Golgi destruction decreases cell adhesion and migration via the reduction of α5β1 integrin.

Mol Biol Cell 2019 Jan 16:mbcE18070462. Epub 2019 Jan 16.

Department of Molecular, Cellular and Developmental Biology, University of Michigan, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA.

The Golgi apparatus is a membrane-bound organelle that serves as the center for trafficking and processing of proteins and lipids. To perform these functions, the Golgi forms a multi-layer stacked structure held by GRASP55 and GRASP65 trans-oligomers and perhaps their binding partners. Depletion of GRASP proteins disrupts Golgi stack formation and impairs critical functions of the Golgi, such as accurate protein glycosylation and sorting. Read More

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http://dx.doi.org/10.1091/mbc.E18-07-0462DOI Listing
January 2019

Colloid osmotic parameterization and measurement of subcellular crowding.

Authors:
T J Mitchison

Mol Biol Cell 2019 Jan;30(2):173-180

Marine Biological Laboratory, Woods Hole, MA 02543.

Crowding of the subcellular environment by macromolecules is thought to promote protein aggregation and phase separation. A challenge is how to parameterize the degree of crowding of the cell interior or artificial solutions that is relevant to these reactions. Here I review colloid osmotic pressure as a crowding metric. Read More

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https://www.molbiolcell.org/doi/10.1091/mbc.E18-09-0549
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http://dx.doi.org/10.1091/mbc.E18-09-0549DOI Listing
January 2019
4 Reads

How the cell cycle clock ticks.

Mol Biol Cell 2019 Jan;30(2):169-172

Institute of Technology, University of Tartu, 50411 Tartu, Estonia.

Eukaryotic cell division has been studied thoroughly and is understood in great mechanistic detail. Paradoxically, however, we lack an understanding of its core control process, in which the master regulator of the cell cycle, cyclin-dependent kinase (CDK), temporally coordinates an array of complex molecular events. The core elements of the CDK control system are conserved in eukaryotic cells, which contain multiple cyclin-CDK forms that have poorly defined and partially overlapping responsibilities in the cell cycle. Read More

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http://dx.doi.org/10.1091/mbc.E18-05-0272DOI Listing
January 2019

Neuronal drebrin A directly interacts with mDia2 formin to inhibit actin assembly.

Mol Biol Cell 2019 Jan 9:mbcE18100639. Epub 2019 Jan 9.

Department of Chemistry and Biochemistry, UCLA, Los Angeles, California, 90095, USA.

Dendritic spines (DS) are actin-rich postsynaptic terminals of neurons that are critical for higher order brain functions. Maturation of DS is accompanied by a change in actin architecture from linear to branched filamentous structures. Presumably, the underlying cause of this is a switch in a mode of actin assembly from formin-driven to Arp2/3-mediated via an undefined mechanism. Read More

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http://dx.doi.org/10.1091/mbc.E18-10-0639DOI Listing
January 2019
1 Read

Expression of TorsinA in a heterologous yeast system reveals interactions with lumenal domains of LINC and nuclear pore complex components.

Mol Biol Cell 2019 Jan 9:mbcE18090585. Epub 2019 Jan 9.

Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.

DYT1 dystonia is caused by an in-frame deletion of a glutamic acid codon in the gene encoding the AAA+ ATPase TorsinA. TorsinA localizes within the lumen of the nuclear envelope/ER and binds to a membrane-spanning co-factor, LAP1 or LULL1, to form an ATPase; the substrate(s) of TorsinA remain ill defined. Here we use budding yeast, which lack Torsins, to interrogate TorsinA function. Read More

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http://dx.doi.org/10.1091/mbc.E18-09-0585DOI Listing
January 2019

Role of JAM-A tyrosine phosphorylation in epithelial barrier dysfunction during intestinal inflammation.

Mol Biol Cell 2019 Jan 9:mbcE18080531. Epub 2019 Jan 9.

Department of Pathology, University of Michigan, Ann Arbor, USA.

Junctional adhesion molecule-A (JAM-A), an epithelial tight junction protein, plays an important role in regulating intestinal permeability through association with a scaffold signaling complex containing ZO-2, Afadin and the small GTPase Rap2. Under inflammatory conditions, we report that the cytoplasmic tail of JAM-A is tyrosine phosphorylated (p-Y280) in association with loss of barrier function. While barely detectable Y280 phosphorylation was observed in confluent monolayers of human intestinal epithelial cells under basal conditions, exposure to cytokines TNFα, IFNγ, IL-22 or IL-17A, resulted in compromised barrier function in parallel with increased p-Y280. Read More

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http://dx.doi.org/10.1091/mbc.E18-08-0531DOI Listing
January 2019
1 Read

Compositional reorganization of the nucleolus in budding yeast mitosis.

Mol Biol Cell 2019 Jan 9:mbcE18080524. Epub 2019 Jan 9.

Department of Genetics, University of Regensburg, D-93040 Regensburg, Germany.

The nucleolus is a membrane-less organelle of the nucleus and the site of ribosomal RNA synthesis, maturation and assembly into pre-ribosomal particles. The nucleolus, organized around arrays of ribosomal RNA genes (rDNA), dissolves during prophase of mitosis in metazoans, when rDNA transcription ceases, and reforms in telophase, when rDNA transcription resumes. No such dissolution and reformation cycle exists in budding yeast, and the precise course of nucleolar segregation remains unclear. Read More

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http://dx.doi.org/10.1091/mbc.E18-08-0524DOI Listing
January 2019

Effects of altering histone post-translational modifications on mitotic chromosome structure and mechanics.

Mol Biol Cell 2019 Jan 9:mbcE18090592. Epub 2019 Jan 9.

Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208.

During cell division chromatin is compacted into mitotic chromosomes to aid faithful segregation of the genome between two daughter cells. Post-translational modifications (PTM) of histones alter compaction of interphase chromatin, but it remains poorly understood how these modifications affect mitotic chromosome stiffness and structure. Using micropipette-based force measurements and epigenetic drugs, we probed the influence of canonical histone PTMs that dictate interphase euchromatin (acetylation) and heterochromatin (methylation) on mitotic chromosome stiffness. Read More

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http://dx.doi.org/10.1091/mbc.E18-09-0592DOI Listing
January 2019

Thiol stress-dependent aggregation of the glycolytic enzyme triose phosphate isomerase in yeast and human cells.

Mol Biol Cell 2019 Jan 2:mbcE18100616. Epub 2019 Jan 2.

Department of Microbiology and Molecular Genetics, University of Texas McGovern Medical School at Houston, Houston TX 77030.

The eukaryotic cytosolic proteome is vulnerable to changes in proteostatic and redox balance caused by temperature, pH, oxidants and xenobiotics. Cysteine-containing proteins are especially at risk as the thiol side chain is subject to oxidation, adduction and chelation by thiol-reactive compounds. The thiol-chelating heavy metal cadmium is a highly toxic environmental pollutant demonstrated to induce the heat shock response and recruit protein chaperones to sites of presumed protein aggregation in the budding yeast Saccharomyces cerevisiae. Read More

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http://dx.doi.org/10.1091/mbc.E18-10-0616DOI Listing
January 2019
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Clathrin plaques and associated actin anchor intermediate filaments in skeletal muscle.

Mol Biol Cell 2019 Jan 2:mbcE18110718. Epub 2019 Jan 2.

Sorbonne Université, INSERM, Institute of Myology, Centre of Research in Myology, UMRS 974, F-75013, Paris, France.

Clathrin plaques are stable features of the plasma membrane observed in several cell types. They are abundant in muscle, where they localize at costameres which link the contractile apparatus to the sarcolemma and connect the sarcolemma to the basal lamina. Here, we show that clathrin plaques and surrounding branched actin filaments form microdomains which anchor a three-dimensional desmin intermediate filament web. Read More

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https://www.molbiolcell.org/doi/10.1091/mbc.E18-11-0718
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http://dx.doi.org/10.1091/mbc.E18-11-0718DOI Listing
January 2019
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Tail domains of myosin-1e regulate phosphatidylinositol signaling and F-actin polymerization at the ventral layer of podosomes.

Mol Biol Cell 2019 Jan 2:mbcE18060398. Epub 2019 Jan 2.

School of Biomedical Sciences, Faculty of Medicine, University of Hong Kong, Hong Kong.

During the podosome formation, distinct phosphatidylinositol 3,4,5-trisphosphate lipid (PI(3,4,5)P3) production and F-actin polymerization take place at integrin-mediated adhesions. Membrane-associated actin regulation factors, such as myosin-1, serve as key molecules to link phosphatidylinositol signals to podosome assembly. Here, we report that long-tailed myosin-1e (Myo1e) is enriched at the ventral layer of the podosome core in a PI(3,4,5)P3 dependent manner. Read More

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http://dx.doi.org/10.1091/mbc.E18-06-0398DOI Listing
January 2019

Ena/VASP processive elongation is modulated by avidity on actin filaments bundled by the filopodia crosslinker fascin.

Mol Biol Cell 2019 Jan 2:mbcE18080500. Epub 2019 Jan 2.

Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637.

Ena/VASP tetramers are processive actin elongation factors that localize to diverse F-actin networks composed of filaments bundled by different crosslinking proteins, such as filopodia (fascin), lamellipodia (fimbrin), and stress fibers (α-actinin). Previously, we found that Ena takes ∼3-fold longer processive runs on trailing barbed ends of fascin-bundled F-actin. Here, we used single-molecule TIRFM and developed a kinetic model to further dissect Ena/VASP's processive mechanism on bundled filaments. Read More

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http://dx.doi.org/10.1091/mbc.E18-08-0500DOI Listing
January 2019
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salto/CG13164 is required for sperm head morphogenesis in Drosophila.

Mol Biol Cell 2019 Jan 2:mbcE18070429. Epub 2019 Jan 2.

Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR-5310, INSERM U-1217, Institut NeuroMyoGène, F-69008, Lyon, France.

Producing mature spermatozoa is essential for sexual reproduction in metazoans. Spermiogenesis involves dramatic cell morphological changes going from sperm tail elongation, nuclear reshaping to cell membrane remodeling during sperm individualization and release. The sperm manchette plays a critical scaffolding function during nuclear remodeling by linking the nuclear lamina to the cytoskeleton. Read More

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http://dx.doi.org/10.1091/mbc.E18-07-0429DOI Listing
January 2019
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Dual RXR motifs regulate NGF-mediated intracellular retention of the delta opioid receptor.

Mol Biol Cell 2019 Jan 2:mbcE18050292. Epub 2019 Jan 2.

Department of Biological Sciences, The Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA 15213, USA.

The delta opioid receptor (DOR), a physiologically relevant prototype for G protein-coupled receptors (GPCRs), is retained in intracellular compartments in neuronal cells. This retention is mediated by an NGF-regulated checkpoint that delays the export of DOR from the Trans-Golgi Network (TGN). How DOR is selectively retained in the Golgi, in the midst of dynamic membrane transport and cargo export, is a fundamental unanswered question. Read More

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http://dx.doi.org/10.1091/mbc.E18-05-0292DOI Listing
January 2019

FBXW7 regulates endothelial barrier function by suppression of the cholesterol synthesis pathway and prenylation of RhoB.

Mol Biol Cell 2019 Jan 2:mbcE18040259. Epub 2019 Jan 2.

Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, location VUmc, Amsterdam, The Netherlands.

Rho GTPases control both the actin cytoskeleton and adherens junction stability and are recognized as essential regulators of endothelial barrier function. Rho GTPases act as molecular switches and are primarily regulated by the exchange of GDP and GTP. However, post-translational modifications such as phosphorylation, prenylation and ubiquitination can additionally alter their localization, stability and activity. Read More

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http://dx.doi.org/10.1091/mbc.E18-04-0259DOI Listing
January 2019
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A nostalgic look back 40 years after the discovery of receptor-mediated endocytosis.

Authors:
Sandra L Schmid

Mol Biol Cell 2019 Jan;30(1):1-3

Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390.

The concept of receptor-mediated endocytosis was proposed 40 years ago in a seminal review by Joseph Goldstein, Michael Brown, and Richard Anderson. Not only their hypothesis but also the lessons learned that guided their discovery have stood the test of time. I recount some of these herein, while also looking back nostalgically at a forgotten era of scientific communication. Read More

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http://dx.doi.org/10.1091/mbc.E18-06-0409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337915PMC
January 2019

Dissociation of membrane-chromatin contacts is required for proper chromosome segregation in mitosis.

Mol Biol Cell 2019 Feb 26;30(4):427-440. Epub 2018 Dec 26.

Department of Biology, Institute of Biochemistry, ETH Zurich, CH-8093 Zurich, Switzerland.

The nuclear envelope (NE) aids in organizing the interphase genome by tethering chromatin to the nuclear periphery. During mitotic entry, NE-chromatin contacts are broken. Here, we report on the consequences of impaired NE removal from chromatin for cell division of human cells. Read More

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http://dx.doi.org/10.1091/mbc.E18-10-0609DOI Listing
February 2019

Ate1-mediated posttranslational arginylation affects substrate adhesion and cell migration in Dictyostelium discoideum.

Mol Biol Cell 2019 Feb 26;30(4):453-466. Epub 2018 Dec 26.

Department of Cell Biology (Anatomy III), Ludwig Maximilian University of Munich, 82152 Planegg-Martinsried, Germany.

The highly conserved enzyme arginyl-tRNA-protein transferase (Ate1) mediates arginylation, a posttranslational modification that is only incompletely understood at its molecular level. To investigate whether arginylation affects actin-dependent processes in a simple model organism, Dictyostelium discoideum, we knocked out the gene encoding Ate1 and characterized the phenotype of ate1-null cells. Visualization of actin cytoskeleton dynamics by live-cell microscopy indicated significant changes in comparison to wild-type cells. Read More

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http://dx.doi.org/10.1091/mbc.E18-02-0132DOI Listing
February 2019

Combining near-infrared fluorescence with Brainbow to visualize expression of specific genes within a multicolor context.

Mol Biol Cell 2019 Feb 26;30(4):491-505. Epub 2018 Dec 26.

Biology Department, Lewis and Clark College, Portland, OR 97219.

Fluorescent proteins are a powerful experimental tool, allowing the visualization of gene expression and cellular behaviors in a variety of systems. Multicolor combinations of fluorescent proteins, such as Brainbow, have expanded the range of possible research questions and are useful for distinguishing and tracking cells. The addition of a separately driven color, however, would allow researchers to report expression of a manipulated gene within the multicolor context to investigate mechanistic effects. Read More

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http://dx.doi.org/10.1091/mbc.E18-06-0340DOI Listing
February 2019