366 results match your criteria CellBio


A Unified Model for Treadmilling and Nucleation of Single-Stranded FtsZ Protofilaments.

Biophys J 2020 08 17;119(4):792-805. Epub 2020 Jul 17.

Department of Biomedical Engineering, Duke University, Durham, North Carolina; Department of Cell Biology, Duke University, Durham, North Carolina. Electronic address:

Bacterial cell division is tightly coupled to the dynamic behavior of FtsZ, a tubulin homolog. Recent experimental work in vitro and in vivo has attributed FtsZ's assembly dynamics to treadmilling, in which subunits add to the bottom and dissociate from the top of protofilaments. However, the molecular mechanisms producing treadmilling have yet to be characterized and quantified. Read More

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Histotopography of α-Gustdusin- and T2R3-Expressing Lymphocytes in Mouse Spleen.

Bull Exp Biol Med 2019 Oct 26;167(6):801-804. Epub 2019 Oct 26.

Udmurt State University, Izhevsk, Russia.

Histotopography of lymphocytes expressing bitter taste receptors of T2R family and α-gustducin (receptor-associated subunit of the G-protein complex) in mouse spleen in the norm and in 48 h after intraperitoneal administration of LPS was studied by the immunohistochemical method. Two populations of immunopositive lymphocytes expressing the above proteins were detected in the spleen; they were located in the marginal zones of lymphoid follicles and periarteriolar lymphoid sheaths. In most α-gustducin-positive lymphocytes, co-expression of α-gustducin and CD19 (B-cell marker) was found. Read More

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October 2019

Changes in Membrane Ceramide Pools in Rat Soleus Muscle in Response to Short-Term Disuse.

Int J Mol Sci 2019 Sep 30;20(19). Epub 2019 Sep 30.

Department of Pathophysiology and Immunology, Izhevsk State Medical Academy, Kommunarov St. 281, 426034 Izhevsk, Russia.

Lipid raft disruption is an early event during skeletal muscle unloading. Ceramide (Cer) serves as a signaling lipid that can contribute to lipid raft disturbance and muscle atrophy. Using biochemical and fluorescent approaches, the distribution of Cer and related molecules in the rat soleus muscle subjected to 12 h of hindlimb suspension (HS) was studied. Read More

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September 2019

Germline-Activating RRAS2 Mutations Cause Noonan Syndrome.

Am J Hum Genet 2019 06 23;104(6):1233-1240. Epub 2019 May 23.

Department of Medical Genetics, Tohoku University School of Medicine, Sendai 980-8574, Japan.

Noonan syndrome (NS) is characterized by distinctive craniofacial appearance, short stature, and congenital heart disease. Approximately 80% of individuals with NS harbor mutations in genes whose products are involved in the RAS/mitogen-activating protein kinase (MAPK) pathway. However, the underlying genetic causes in nearly 20% of individuals with NS phenotype remain unexplained. Read More

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Microtubule Assembly from Single Flared Protofilaments-Forget the Cozy Corner?

Biophys J 2019 06 8;116(12):2240-2245. Epub 2019 May 8.

Departments of Cell Biology, Biochemistry, and Biomedical Engineering, Duke University Medical Center, Durham, North Carolina. Electronic address:

A paradigm shift for models of MT assembly is suggested by a recent cryo-electron microscopy study of microtubules (MTs). Previous assembly models have been based on the two-dimensional lattice of the MT wall, where incoming subunits can add with longitudinal and lateral bonds. The new study of McIntosh et al. Read More

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Mutations in ATP13A2 (PARK9) are associated with an amyotrophic lateral sclerosis-like phenotype, implicating this locus in further phenotypic expansion.

Hum Genomics 2019 04 16;13(1):19. Epub 2019 Apr 16.

Center for Human Disease Modeling, Duke University Medical Center, Carmichael Building, 300 North Duke Street, Suite 48-118, Durham, NC, 27701, USA.

Background: Amyotrophic lateral sclerosis [1] is a genetically heterogeneous neurodegenerative disorder, characterized by late-onset degeneration of motor neurons leading to progressive limb and bulbar weakness, as well as of the respiratory muscles, which is the primary cause of disease fatality. To date, over 25 genes have been implicated as causative in ALS with C9orf72, SOD1, FUS, and TARDBP accounting for the majority of genetically positive cases.

Results: We identified two patients of Italian and French ancestry with a clinical diagnosis of juvenile-onset ALS who were mutation-negative in any of the known ALS causative genes. Read More

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Flax tubulin and CesA superfamilies represent attractive and challenging targets for a variety of genome- and base-editing applications.

Funct Integr Genomics 2020 Jan 2;20(1):163-176. Epub 2019 Mar 2.

Istituto di Biologia e Biotecnologia Agraria IBBA-CNR, Via Alfonso Corti 12, 20133, Milan, Italy.

Flax is both a valuable resource and an interesting model crop. Despite a long history of flax genetic transformation only one transgenic linseed cultivar has been so far registered in Canada. Implementation and use of the genome-editing technologies that allow site-directed modification of endogenous genes without the introduction of foreign genes might improve this situation. Read More

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January 2020

Molecular Pathogenesis in Huntington's Disease.

Biochemistry (Mosc) 2018 Sep;83(9):1030-1039

Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia.

Huntington's disease (HD) is a severe autosomal dominant neurodegenerative disorder characterized by a combination of motor, cognitive, and psychiatric symptoms, atrophy of the basal ganglia and the cerebral cortex, and inevitably progressive course resulting in death 5-20 years after manifestation of its symptoms. HD is caused by expansion of CAG repeats in the HTT gene, which leads to pathological elongation of the polyglutamine tract within the respective protein - huntingtin. In this review, we present a modern view on molecular biology of HD as a representative of the group of polyglutamine diseases, with an emphasis on conformational changes of mutant huntingtin, disturbances in its cellular processing, and proteolytic stress in degenerating neurons. Read More

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September 2018

Tissue self-organization underlies morphogenesis of the notochord.

Philos Trans R Soc Lond B Biol Sci 2018 09 24;373(1759). Epub 2018 Sep 24.

Department of Cell Biology, Duke University, Durham, NC 27710, USA

The notochord is a conserved axial structure that in vertebrates serves as a hydrostatic scaffold for embryonic axis elongation and, later on, for proper spine assembly. It consists of a core of large fluid-filled vacuolated cells surrounded by an epithelial sheath that is encased in extracellular matrix. During morphogenesis, the vacuolated cells inflate their vacuole and arrange in a stereotypical staircase pattern. Read More

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September 2018

Transcriptome analysis supports viral infection and fluoride toxicity as contributors to chronic kidney disease of unknown etiology (CKDu) in Sri Lanka.

Int Urol Nephrol 2018 Sep 28;50(9):1667-1677. Epub 2018 May 28.

Molecular Microbiology and Human Diseases, National Institute of Fundamental Studies, Kandy, 20000, Sri Lanka.

Purpose: Chronic kidney disease of unknown etiology (CKDu), having epidemic characteristics, is being diagnosed increasingly in certain tropical regions of the world, mainly Latin America and Sri Lanka. They have been observed primarily in farming communities and current hypotheses point toward many environmental and occupational triggers. CKDu does not have common etiologies of chronic kidney disease (CKD) such as hypertension, diabetes, or autoimmune disease. Read More

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September 2018

The cell division protein MinD from dominates the assembly of the MinC-MinD copolymers.

J Biol Chem 2018 05 2;293(20):7786-7795. Epub 2018 Apr 2.

From the Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, Shaanxi, China 710069 and

Cell division of rod-shaped bacteria requires the Z ring, a ring of FtsZ filaments associated with the inner-membrane wall. The MinCDE proteins help localize the Z ring to the center of the cell. MinC, which inhibits Z-ring assembly, is a passenger on MinD. Read More

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Spine Patterning Is Guided by Segmentation of the Notochord Sheath.

Cell Rep 2018 02;22(8):2026-2038

Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Regeneration Next, Duke University, Durham, NC 27710, USA. Electronic address:

The spine is a segmented axial structure made of alternating vertebral bodies (centra) and intervertebral discs (IVDs) assembled around the notochord. Here, we show that, prior to centra formation, the outer epithelial cell layer of the zebrafish notochord, the sheath, segments into alternating domains corresponding to the prospective centra and IVD areas. This process occurs sequentially in an anteroposterior direction via the activation of Notch signaling in alternating segments of the sheath, which transition from cartilaginous to mineralizing domains. Read More

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February 2018

Myosin II sequences for Lethocerus indicus.

J Muscle Res Cell Motil 2017 04 13;38(2):193-200. Epub 2017 Jul 13.

Department of Cell Biology, Duke University, Box 3011, Durham, NC, 27705, USA.

We present the genomic and expressed myosin II sequences from the giant waterbug, Lethocerus indicus. The intron rich gene appears relatively ancient and contains six regions of mutually exclusive exons that are alternatively spliced. Alternatively spliced regions may be involved in the asymmetric myosin dimer structure known as the interacting heads motif, as well as stabilizing the interacting heads motif within the thick filament. Read More

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Sheath Cell Invasion and Trans-differentiation Repair Mechanical Damage Caused by Loss of Caveolae in the Zebrafish Notochord.

Curr Biol 2017 Jul 22;27(13):1982-1989.e3. Epub 2017 Jun 22.

Department of Cell Biology, Duke University, Durham, NC 27710, USA. Electronic address:

The notochord, a conserved axial structure required for embryonic axis elongation and spine development, consists of giant vacuolated cells surrounded by an epithelial sheath [1-3]. During morphogenesis, vacuolated cells maintain their structural integrity despite being under constant mechanical stress [4]. We hypothesized that the high density of caveolae present in vacuolated cells [5, 6] could buffer mechanical tension. Read More

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FtsZ Constriction Force - Curved Protofilaments Bending Membranes.

Subcell Biochem 2017;84:139-160

Department of Cell Biology, Duke University, Durham, NC, 27710, USA.

FtsZ assembles in vitro into protofilaments (pfs) that are one subunit thick and ~50 subunits long. In vivo these pfs assemble further into the Z ring, which, along with accessory division proteins, constricts to divide the cell. We have reconstituted Z rings in liposomes in vitro, using pure FtsZ that was modified with a membrane targeting sequence to directly bind the membrane. Read More

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Mutations in TMEM260 Cause a Pediatric Neurodevelopmental, Cardiac, and Renal Syndrome.

Am J Hum Genet 2017 Apr 16;100(4):666-675. Epub 2017 Mar 16.

Center for Human Disease Modeling, Duke University Medical Center, Durham, NC 27701, USA.

Despite the accelerated discovery of genes associated with syndromic traits, the majority of families affected by such conditions remain undiagnosed. Here, we employed whole-exome sequencing in two unrelated consanguineous kindreds with central nervous system (CNS), cardiac, renal, and digit abnormalities. We identified homozygous truncating mutations in TMEM260, a locus predicted to encode numerous splice isoforms. Read More

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The Chloroplast Tubulin Homologs FtsZA and FtsZB from the Red Alga Co-assemble into Dynamic Filaments.

J Biol Chem 2017 03 7;292(13):5207-5215. Epub 2017 Feb 7.

the Department of Cell Biology, Duke University School of Medicine, Durham, North Carolina 27710-3709, and

FtsZ is a homolog of eukaryotic tubulin and is present in almost all bacteria and many archaea, where it is the major cytoskeletal protein in the Z ring, required for cell division. Unlike some other cell organelles of prokaryotic origin, chloroplasts have retained FtsZ as an essential component of the division machinery. However, chloroplast FtsZs have been challenging to study because they are difficult to express and purify. Read More

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The discovery of the prokaryotic cytoskeleton: 25th anniversary.

Mol Biol Cell 2017 Feb;28(3):357-358

Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710-3709

The year 2017 marks the 25th anniversary of the discovery of homologues of tubulin and actin in prokaryotes. Before 1992, it was largely accepted that tubulin and actin were unique to eukaryotes. Then three laboratories independently discovered that FtsZ, a protein already known as a key player in bacterial cytokinesis, had the "tubulin signature sequence" present in all α-, β-, and γ-tubulins. Read More

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February 2017

Protein unfolding under isometric tension-what force can integrins generate, and can it unfold FNIII domains?

Curr Opin Struct Biol 2017 02 27;42:98-105. Epub 2016 Dec 27.

Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:

Extracellular matrix fibrils of fibronectin (FN) are highly elastic, and are typically stretched three to four times their relaxed length. The mechanism of stretching has been controversial, in particular whether it involves tension-induced unfolding of FNIII domains. Recent studies have found that ∼5pN is the threshold isometric force for unfolding various protein domains. Read More

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February 2017

Spontaneous Unfolding-Refolding of Fibronectin Type III Domains Assayed by Thiol Exchange: THERMODYNAMIC STABILITY CORRELATES WITH RATES OF UNFOLDING RATHER THAN FOLDING.

J Biol Chem 2017 01 30;292(3):955-966. Epub 2016 Nov 30.

From the Departments of Biochemistry and

Globular proteins are not permanently folded but spontaneously unfold and refold on time scales that can span orders of magnitude for different proteins. A longstanding debate in the protein-folding field is whether unfolding rates or folding rates correlate to the stability of a protein. In the present study, we have determined the unfolding and folding kinetics of 10 FNIII domains. Read More

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January 2017

Probing for Binding Regions of the FtsZ Protein Surface through Site-Directed Insertions: Discovery of Fully Functional FtsZ-Fluorescent Proteins.

J Bacteriol 2017 01 13;199(1). Epub 2016 Dec 13.

Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, USA

FtsZ, a bacterial tubulin homologue, is a cytoskeletal protein that assembles into protofilaments that are one subunit thick. These protofilaments assemble further to form a "Z ring" at the center of prokaryotic cells. The Z ring generates a constriction force on the inner membrane and also serves as a scaffold to recruit cell wall remodeling proteins for complete cell division in vivo One model of the Z ring proposes that protofilaments associate via lateral bonds to form ribbons; however, lateral bonds are still only hypothetical. Read More

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January 2017

Real time PCR for the rapid identification and drug susceptibility of Mycobacteria present in Bronchial washings.

BMC Infect Dis 2016 Oct 26;16(1):607. Epub 2016 Oct 26.

Department of Molecular Biology and Biotechnology, University of Peradeniya, Peradeniya, Sri Lanka.

Background: Mycobacteria have a spectrum of virulence and different susceptibilities to antibiotics. Distinguishing mycobacterial species is vital as patients with non-tuberculous mycobacterial (NTM) infections present clinical features that are similar to those of patients with tuberculosis. Thus, rapid differentiation of Mycobacterium tuberculosis complex from NTM is critical to administer appropriate treatment. Read More

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October 2016

Copy-Number Variation Contributes to the Mutational Load of Bardet-Biedl Syndrome.

Am J Hum Genet 2016 08;99(2):318-36

Center for Human Disease Modeling, Duke University School of Medicine, Durham, NC 27701, USA. Electronic address:

Bardet-Biedl syndrome (BBS) is a defining ciliopathy, notable for extensive allelic and genetic heterogeneity, almost all of which has been identified through sequencing. Recent data have suggested that copy-number variants (CNVs) also contribute to BBS. We used a custom oligonucleotide array comparative genomic hybridization (aCGH) covering 20 genes that encode intraflagellar transport (IFT) components and 74 ciliopathy loci to screen 92 unrelated individuals with BBS, irrespective of their known mutational burden. Read More

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Mitochondrial Copy Number as a Biomarker for Autism?

Pediatrics 2016 04 31;137(4). Epub 2016 Mar 31.

Center for Human Disease Modeling, Duke University School of Medicine, Durham, North Carolina

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Human Macrophages Utilize the Podosome Formin FMNL1 for Adhesion and Migration.

Cellbio (Irvine, Calif) 2015 Mar 4;4(1):1-11. Epub 2015 Mar 4.

Department of Cell & Developmental Biology, SUNY Upstate Medical University, New York, USA.

Macrophages play a crucial role in detecting, regulating, and resolving immune crises, requiring migration through complex extracellular matrices. Unwarranted macrophage inflammatory activity potentiates kidney disease, rheumatoid arthritis, and transplant rejection. Proper remodeling of the actin cytoskeleton, especially at adhesion structures, is essential to the translocation of macrophages. Read More

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Human Umbilical Tissue-Derived Cells Promote Synapse Formation and Neurite Outgrowth via Thrombospondin Family Proteins.

J Neurosci 2015 Nov;35(47):15649-65

Departments of Cell Biology, Neurobiology, Duke Institute for Brain Sciences, Duke University, Durham, North Carolina 27710, and

Unlabelled: Cell therapy demonstrates great potential for the treatment of neurological disorders. Human umbilical tissue-derived cells (hUTCs) were previously shown to have protective and regenerative effects in animal models of stroke and retinal degeneration, but the underlying therapeutic mechanisms are unknown. Because synaptic dysfunction, synapse loss, degeneration of neuronal processes, and neuronal death are hallmarks of neurological diseases and retinal degenerations, we tested whether hUTCs contribute to tissue repair and regeneration by stimulating synapse formation, neurite outgrowth, and neuronal survival. Read More

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November 2015

Newborn screening and the era of medical genomics.

Semin Perinatol 2015 Dec 21;39(8):617-22. Epub 2015 Oct 21.

Center for Human Disease Modeling, Duke University School of Medicine, 300 N Duke St, Durham, NC 27701. Electronic address:

Across the span of the last 75+ years, technological and conceptual advances in genetics have found rapid implementation at the beginning of human life. From karyotype testing, to molecular cytogenetics, to gene panel testing, and now to whole exome and whole genome sequencing, each iterative expansion of our capability to acquire genetic data on the next generation has been implemented quickly in the clinical setting. In tandem, our continuously expanding ability to acquire large volumes of genetic data has generated its own challenges in terms of interpretation, clinical utility of the information, and concerns over privacy and discrimination; for the first time, we are faced with the possibility of having complete access to our genetic data from birth, if not shortly after conception. Read More

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December 2015

A Potential Contributory Role for Ciliary Dysfunction in the 16p11.2 600 kb BP4-BP5 Pathology.

Am J Hum Genet 2015 May 30;96(5):784-96. Epub 2015 Apr 30.

Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland. Electronic address:

The 16p11.2 600 kb copy-number variants (CNVs) are associated with mirror phenotypes on BMI, head circumference, and brain volume and represent frequent genetic lesions in autism spectrum disorders (ASDs) and schizophrenia. Here we interrogated the transcriptome of individuals carrying reciprocal 16p11. Read More

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Stepping between membrane microdomains.

Biophys J 2015 Feb;108(4):783-784

Department of Cell Biology, Duke University Medical Center, Durham, North Carolina. Electronic address:

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February 2015

Chronic fluoxetine increases extra-hippocampal neurogenesis in adult mice.

Int J Neuropsychopharmacol 2014 Oct 31;18(4). Epub 2014 Oct 31.

Department of Cell Biology, Duke University Medical Center, Durham, NC (Drs Sachs and Caron); Department of Neurobiology, Duke University Medical Center, Durham, NC (Dr Caron).

Background: Chronic treatment with antidepressants has been shown to enhance neurogenesis in the adult mammalian brain. Although this effect was initially reported to be restricted to the hippocampus, recent work has suggested that fluoxetine, a selective serotonin reuptake inhibitor, also promotes neurogenesis in the cortex. However, whether antidepressants target neural progenitor cells in other brain regions has not been examined. Read More

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October 2014