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Canine Parvovirus Infections in Taiwanese Pangolins ().

Vet Pathol 2021 Apr 19:3009858211002198. Epub 2021 Apr 19.

National Chung Hsing University, Taichung.

Canine parvovirus type 2 (CPV-2) is among the most important and highly contagious pathogens that cause enteric or systemic infections in domestic and nondomestic carnivores. However, the spillover of CPV-2 to noncarnivores is rarely mentioned. Taiwanese pangolins () are threatened due to habitat fragmentation and prevalent animal trafficking. Read More

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Tombusviruses orchestrate the host endomembrane system to create elaborate membranous replication organelles.

Curr Opin Virol 2021 Apr 9;48:30-41. Epub 2021 Apr 9.

Department of Plant Pathology, University of Kentucky, Lexington, KY 40546, USA.

Positive-strand RNA viruses depend on intensive manipulation of subcellular organelles and membranes to create unique viral replication organelles (VROs), which represent the sites of robust virus replication. The host endomembrane-based protein-trafficking and vesicle-trafficking pathways are specifically targeted by many (+)RNA viruses to take advantage of their rich resources. We summarize the critical roles of co-opted endoplasmic reticulum subdomains and associated host proteins and COPII vesicles play in tombusvirus replication. Read More

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IgG intrathecal synthesis in HIV-associated neurocognitive disorder (HAND) according to the HIV-1 subtypes and pattern of HIV RNA in CNS and plasma compartments.

J Neuroimmunol 2021 Mar 8;355:577542. Epub 2021 Mar 8.

HIV Neurobehavioral Research Center, University of California, San Diego, San Diego, CA, USA.

We hypothesized that humoral immunity stimulation in the CNS in HIV-1C patients would be lower than that in HIV-1B due to a defective Tat chemokine dimotif (C30C31) that might influence cellular trafficking and CNS inflammation. Sixty-eight paired CSF and blood samples from people with HIV (PWH), free of CNS opportunistic infections, were included, HIV-1B (n = 27), HIV-1C (n = 26), and HIV negative (n = 25). IgG intrathecal synthesis was assayed using quantitative and qualitative methods. Read More

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Structural biology of coronavirus ion channels.

Acta Crystallogr D Struct Biol 2021 Apr 3;77(Pt 4):391-402. Epub 2021 Mar 3.

Biomedical Research Institute (BIOMED), Catholic University of Argentina (UCA) - National Scientific and Technical Research Council (CONICET), C1107AFF Buenos Aires, Argentina.

Viral infection compromises specific organelles of the cell and readdresses its functional resources to satisfy the needs of the invading body. Around 70% of the coronavirus positive-sense single-stranded RNA encodes proteins involved in replication, and these viruses essentially take over the biosynthetic and transport mechanisms to ensure the efficient replication of their genome and trafficking of their virions. Some coronaviruses encode genes for ion-channel proteins - the envelope protein E (orf4a), orf3a and orf8 - which they successfully employ to take control of the endoplasmic reticulum-Golgi complex intermediate compartment or ERGIC. Read More

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Zipcode RNA-Binding Proteins and Membrane Trafficking Proteins Cooperate to Transport Glutelin mRNAs in Rice Endosperm.

Plant Cell 2020 Aug;32(8):2566-2581

Institute of Biological Chemistry, Washington State University, Pullman, Washington 99164-6340.

In rice (Oryza sativa) endosperm cells, mRNAs encoding glutelin and prolamine are translated on distinct cortical-endoplasmic reticulum (ER) subdomains (the cisternal-ER and protein body-ER), a process that facilitates targeting of their proteins to different endomembrane compartments. Although the cis- and trans-factors responsible for mRNA localization have been defined over the years, how these mRNAs are transported to the cortical ER has yet to be resolved. Here, we show that the two interacting glutelin zipcode RNA binding proteins (RBPs), RBP-P and RBP-L, form a quaternary complex with the membrane fusion factors n-ethylmaleimide-sensitive factor (NSF) and the small GTPase Rab5a, enabling mRNA transport on endosomes. Read More

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Parkinson's Disease Causative Mutation in Vps35 Disturbs Tetherin Trafficking to Cell Surfaces and Facilitates Virus Spread.

Cells 2021 03 28;10(4). Epub 2021 Mar 28.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, characterized by progressive loss of dopaminergic neurons in the substantia nigra, intraneuronal deposition of misfolded proteins known as Lewy bodies, and chronic neuroinflammation. PD can arise from monogenic mutations, but in most cases, the etiology is unclear. Viral infection is gaining increasing attentions as a trigger of PD. Read More

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Rab27a-Dependent Paracrine Communication Controls Dendritic Spine Formation and Sensory Responses in the Barrel Cortex.

Cells 2021 Mar 11;10(3). Epub 2021 Mar 11.

Departments of Neurosurgery, and Cellular & Molecular Physiology, School of Medicine, Yale University, 333 Cedar Street, New Haven, CT 06520-8082, USA.

Rab27a is an evolutionarily conserved small GTPase that regulates vesicle trafficking, and copy number variants of are associated with increased risk of autism. However, the function of Rab27a on brain development is unknown. Here, we identified a form of paracrine communication that regulates spine development between distinct populations of developing cortical neurons. Read More

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Picornaviruses: A View from 3A.

Viruses 2021 Mar 11;13(3). Epub 2021 Mar 11.

Department of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark.

Picornaviruses are comprised of a positive-sense RNA genome surrounded by a protein shell (or capsid). They are ubiquitous in vertebrates and cause a wide range of important human and animal diseases. The genome encodes a single large polyprotein that is processed to structural (capsid) and non-structural proteins. Read More

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Next-generation yeast-two-hybrid analysis with Y2H-SCORES identifies novel interactors of the MLA immune receptor.

PLoS Comput Biol 2021 Apr 2;17(4):e1008890. Epub 2021 Apr 2.

Program in Bioinformatics & Computational Biology, Iowa State University, Ames, Iowa, United States of America.

Protein-protein interaction networks are one of the most effective representations of cellular behavior. In order to build these models, high-throughput techniques are required. Next-generation interaction screening (NGIS) protocols that combine yeast two-hybrid (Y2H) with deep sequencing are promising approaches to generate interactome networks in any organism. Read More

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Cell type-specific biogenesis of novel vesicles containing viral products in human cytomegalovirus infection.

J Virol 2021 Mar 24. Epub 2021 Mar 24.

Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ 85721

Human cytomegalovirus (HCMV), while highly restricted for the human species, infects an diverse array of cell types in the host. Patterns of infection are dictated by the cell type infected, but cell type-specific factors and how they impact tropism for specific cell types is poorly understood. Previous studies in primary endothelial cells showed that HCMV infection induces large multivesicular-like bodies (MVBs) that incorporate viral products, including dense bodies (DBs) and virions. Read More

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Type I T cells sensitize treatment refractory tumors to chemotherapy through inhibition of oncogenic signaling pathways.

J Immunother Cancer 2021 Mar;9(3)

UW Medicine Cancer Vaccine Institute, University of Washington, Seattle, WA, USA.

Background: The most common clinical outcome observed after treatment with immune checkpoint inhibitor antibodies is disease stabilization. Using vaccines to generate high levels of tumor antigen-specific T-helper 1 (Th1), we show that tumors not eradicated by vaccination demonstrate prolonged disease stabilization. We evaluated the mechanism by which type I T cells inhibit disease progression and potentially influence the subsequent clinical response to standard therapy in treatment refractory cancers. Read More

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The lncRNA Snhg1-Vps13D vesicle trafficking system promotes memory CD8 T cell establishment via regulating the dual effects of IL-7 signaling.

Signal Transduct Target Ther 2021 03 24;6(1):126. Epub 2021 Mar 24.

Institute of Immunology PLA, Third Military Medical University, Chongqing, 400038, China.

The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection. Recent studies indicated that long-noncoding RNAs expression is highly cell- and stage-specific during T cell development and differentiation, suggesting their potential roles in T cell programs. However, the key lncRNAs playing crucial roles in memory CD8 T cell establishment remain to be clarified. Read More

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Autophagy inhibition perturbs ERBB2 trafficking and abolishes tumorigenesis in ERBB2-driven breast cancer.

Autophagy 2021 Mar 28:1-2. Epub 2021 Mar 28.

Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Macroautophagy/autophagy modulation is increasingly recognized as a potential strategy for cancer therapy. Using a recently developed mutant knockin mice model, we have taken a rigorous genetic approach to assess the role of both its autophagy and non-canonical functions in an ERBB2-driven BrCA model. We found that autophagy abrogation virtually abolishes mammary tumorigenesis in the ERBB2-driven model, exhibiting stronger inhibitory effects than in our previous studies using PyMT and -null mouse models. Read More

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Cex1 is a component of the COPI intracellular trafficking machinery.

Biol Open 2021 Mar 22;10(3). Epub 2021 Mar 22.

Génétique Moléculaire et Cellulaire, Université de Strasbourg, CNRS, GMGM UMR7156, F-67000 Strasbourg, France.

COPI (coatomer complex I) coated vesicles are involved in Golgi-to-ER and intra-Golgi trafficking pathways, and mediate retrieval of ER resident proteins. Functions and components of the COPI-mediated trafficking pathways, beyond the canonical set of Sec/Arf proteins, are constantly increasing in number and complexity. In mammalian cells, GORAB, SCYL1 and SCYL3 proteins regulate Golgi morphology and protein glycosylation in concert with the COPI machinery. Read More

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Lymphatic Endothelial Cell Activation and Dendritic Cell Transmigration Is Modified by Genetic Deletion of Clever-1.

Front Immunol 2021 4;12:602122. Epub 2021 Mar 4.

MediCity Research Laboratory, University of Turku, Turku, Finland.

Clever-1 also known as Stabilin-1 and FEEL-1 is a scavenger molecule expressed on a subpopulation of anti-inflammatory macrophages and lymphatic endothelial cells (LECs). However, its role in regulating dendritic cell (DC) trafficking and subsequent effects on immunity have remained unexplored. In this study, we demonstrate that DC trafficking from the skin into the draining lymph nodes is compromised in the absence of Clever-1. Read More

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The microtubule-associated protein WDL4 modulates auxin distribution to promote apical hook opening in Arabidopsis.

Plant Cell 2021 Mar 17. Epub 2021 Mar 17.

State Key Laboratory of Plant Physiology and Biochemistry; Department of Plant Sciences, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

The unique apical hook in dicotyledonous plants protects the shoot apical meristem and cotyledons when seedlings emerge through the soil. Its formation involves differential cell growth under the coordinated control of plant hormones, especially ethylene and auxin. Microtubules are an essential player in plant cell growth that are regulated by multiple microtubule-associated proteins (MAPs). Read More

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Ap2s1 mutation causes hypercalcaemia in mice and impairs interaction between calcium-sensing receptor and adaptor protein-2.

Hum Mol Genet 2021 Mar 17. Epub 2021 Mar 17.

Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

Adaptor protein 2 (AP2), a heterotetrameric complex comprising AP2α, AP2β2, AP2μ2 and AP2σ2 subunits, is ubiquitously expressed and involved in endocytosis and trafficking of membrane proteins, such as the calcium-sensing receptor (CaSR), a G-protein coupled receptor that signals via Gα11. Mutations of CaSR, Gα11 and AP2σ2, encoded by AP2S1, cause familial hypocalciuric hypercalcaemia types 1-3 (FHH1-3), respectively. FHH3 patients have heterozygous AP2S1 missense Arg15 mutations (p. Read More

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ALIX and ceramide differentially control polarized small extracellular vesicle release from epithelial cells.

EMBO Rep 2021 Mar 16:e51475. Epub 2021 Mar 16.

Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, Japan.

Exosomes, important players in cell-cell communication, are small extracellular vesicles of endocytic origin. Although single cells are known to release various kinds of exosomes (referred to as exosomal heterogeneity), very little is known about the mechanisms by which they are produced and released. Here, we established methods of studying exosomal heterogeneity by using polarized epithelial cells and showed that distinct types of small extracellular vesicles (more specifically CD9- and CD63-positive, Annexin I-negative small extracellular vesicles, which we refer to as exosomes herein) are differentially secreted from the apical and basolateral sides of polarized epithelial cells. Read More

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Satellite cells deficiency and defective regeneration in dynamin 2-related centronuclear myopathy.

FASEB J 2021 Apr;35(4):e21346

Laboratory of Muscle Proteins and Comparative Histopathology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.

Dynamin 2 (DNM2) is a ubiquitously expressed protein involved in many functions related to trafficking and remodeling of membranes and cytoskeleton dynamics. Mutations in the DNM2 gene cause the autosomal dominant centronuclear myopathy (AD-CNM), characterized mainly by muscle weakness and central nuclei. Several defects have been identified in the KI-Dnm2 mouse model of the disease to explain the muscle phenotype, including reduction of the satellite cell pool in muscle, but the functional consequences of this depletion have not been characterized until now. Read More

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Identification of a Novel Serum Proteomic Signature for Primary Sjögren's Syndrome.

Front Immunol 2021 23;12:631539. Epub 2021 Feb 23.

IRMB, University of Montpellier, INSERM, CHU Montpellier, Montpellier, France.

Context: Primary Sjögren's syndrome (pSS) is a complex heterogeneous autoimmune disease (AID) which can mimic rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Our exploratory study investigated serum biomarkers that may discriminate pSS from RA and SLE.

Methods: Serum concentrations of 63 biomarkers involved in immune cell trafficking, inflammatory response, cellular movement, and cell-to-cell signaling were measured in AID patients, included prospectively into the study at the Montpellier University Hospital. Read More

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February 2021

Effect of conditional deletion of cytoplasmic dynein heavy chain DYNC1H1 on postnatal photoreceptors.

PLoS One 2021 11;16(3):e0248354. Epub 2021 Mar 11.

Department of Ophthalmology, University of Utah Health Science Center, Salt Lake City, Utah, United States of America.

Cytoplasmic dynein (dynein 1), a major retrograde motor of eukaryotic cells, is a 1.4 MDa protein complex consisting of a pair of heavy chains (DYNC1H1) and a set of heterodimeric noncatalytic accessory components termed intermediate, light intermediate and light chains. DYNC1H1 (4644 amino acids) is the dynein backbone encoded by a gene consisting of 77 exons. Read More

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Host-interactor screens of Phytophthora infestans RXLR proteins reveal vesicle trafficking as a major effector-targeted process.

Plant Cell 2021 Mar 2. Epub 2021 Mar 2.

The Sainsbury Laboratory, University of East Anglia, Norwich Research Park, Norwich, United Kingdom.

Pathogens modulate plant cell structure and function by secreting effectors into host tissues. Effectors typically function by associating with host molecules and modulating their activities. This study aimed to identify the host processes targeted by the RXLR class of host-translocated effectors of the potato blight pathogen Phytophthora infestans. Read More

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Drebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking.

Nat Commun 2021 03 5;12(1):1490. Epub 2021 Mar 5.

Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Berlin, Germany.

The brain of mammals lacks a significant ability to regenerate neurons and is thus particularly vulnerable. To protect the brain from injury and disease, damage control by astrocytes through astrogliosis and scar formation is vital. Here, we show that brain injury in mice triggers an immediate upregulation of the actin-binding protein Drebrin (DBN) in astrocytes, which is essential for scar formation and maintenance of astrocyte reactivity. Read More

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Biology and Clinical Applicability of Plasma Thymus and Activation-Regulated Chemokine (TARC) in Classical Hodgkin Lymphoma.

Cancers (Basel) 2021 Feb 20;13(4). Epub 2021 Feb 20.

Department of Pediatric Hemato-oncology, Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.

Thymus and activation-regulated chemokine (TARC) is produced by different cell types and is highly expressed in the thymus. It plays an important role in T cell development, trafficking and activation of mature T cells after binding to its receptor C-C chemokine receptor type 4 (CCR4) and consecutive signal transducer and activator of transcription 6 (STAT6) activation. Importantly, TARC is also produced by malignant Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). Read More

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February 2021

Real-time Three-dimensional Tracking of Endocytic Vesicles.

Bio Protoc 2020 Oct 20;10(20):e3794. Epub 2020 Oct 20.

Department of Biochemistry, McGill University, Montreal, Quebec, Canada.

Endocytic trafficking and recycling are fundamental cellular processes that control essential functions such as signaling protein complexes transport and membrane identity. The small GTPase Rabs are indispensable component of the endosomal recycling machinery. The Rabs bind to effectors to mediate their functions, such as protein sorting and degradation, membrane tethering or lipid modification, and organelle motility. Read More

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October 2020

Protein Interactomes of Streptococcus mutans YidC1 and YidC2 Membrane Protein Insertases Suggest SRP Pathway-Independent- and -Dependent Functions, Respectively.

mSphere 2021 03 3;6(2). Epub 2021 Mar 3.

Department of Oral Biology, University of Florida, Gainesville, Florida, USA

Virulence properties of cariogenic depend on integral membrane proteins. Bacterial cotranslational protein trafficking involves the signal recognition particle (SRP) pathway components Ffh and FtsY, the SecYEG translocon, and YidC chaperone/insertases. Unlike , survives loss of the SRP pathway and has two paralogs. Read More

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Novel ORAI1 Mutation Disrupts Channel Trafficking Resulting in Combined Immunodeficiency.

J Clin Immunol 2021 Mar 1. Epub 2021 Mar 1.

Department of Physiology and Biophysics, Weill Cornell Medicine Qatar, Education City, Qatar Foundation, Doha, Qatar.

Store-operated Ca entry (SOCE) represents a predominant Ca influx pathway in non-excitable cells. SOCE is required for immune cell activation and is mediated by the plasma membrane (PM) channel ORAI1 and the endoplasmic reticulum (ER) Ca sensor STIM1. Mutations in the Orai1 or STIM1 genes abolish SOCE leading to combined immunodeficiency (CID), muscular hypotonia, and anhidrotic ectodermal dysplasia. Read More

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Blue light induces the nuclear translocation of neuropeptide receptor PAC1-R associated with the up-regulation of PAC1-R its own in reactive oxygen species associated way.

Biochim Biophys Acta Gen Subj 2021 Jun 26;1865(6):129884. Epub 2021 Feb 26.

Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, China.

PAC1-R is neuropeptide PACAP (pituitary adenylate cyclase activating polypeptide) preferring receptor mediates the antioxidant and cytoprotective effects of PACAP. It was found in this research that in both PAC1R-CHO cells with high expression of PAC1R-eGFP and retinal ganglion cells (RGC-5) with natural expression of PAC1-R, blue light and hydrogen peroxide (HO) trigger the significant nuclear translocation of PAC1-R, and the nuclear translocation of PAC1-R was positive correlation with the up-regulation of expression level and promoter activity of PAC1-R its own, while red light worked much less efficiently than blue light. Reactive oxygen species (ROS) scavenger NAC (N-acetyl-L-cysteine) and palmitoylation inhibitor 2-bromopalmitate (2-BP) disturbed the nuclear shifting associated with the correlative up-regulation of PAC1 significantly, and PAC1-R mutant (M-PAC1-R) on Cys25/Ala25 displayed the significant decreased nuclear trafficking efficiency. Read More

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Profilin promotes formin-mediated actin filament assembly and vesicle transport during polarity formation in pollen.

Plant Cell 2021 Feb 8. Epub 2021 Feb 8.

Center for Biological Science and Technology, Institute of Natural Science, Beijing Normal University, Zhuhai 519087, China.

Pollen germination is critical for the reproduction of flowering plants. Formin-dependent actin polymerization plays vital roles in vesicle trafficking and polarity establishment during this process. However, how formin-mediated actin assembly is regulated in vivo remains poorly understood. Read More

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February 2021

ALS-causing SOD1 mutants regulate occludin phosphorylation/ubiquitination and endocytic trafficking via the ITCH/Eps15/Rab5 axis.

Neurobiol Dis 2021 Jun 24;153:105315. Epub 2021 Feb 24.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address:

It is increasingly recognized that blood-spinal cord barrier (BSCB) breakdown is a hallmark of amyotrophic lateral sclerosis (ALS). BSCB integrity is disrupted prior to disease onset. Occludin, as the functional component of the endothelial barrier, is downregulated in mouse models expressing ALS-linked superoxide dismutase-1 (SOD1) mutants. Read More

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