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Vesicular trafficking

Min Cai, Jin Chen, Caihua Yu, Lingling Xi, Qin Jiang, Yizhen Wang, Xinxia Wang
Family with Sequence Similarity 134, Member B (FAM134B), is a cis-Golgi transmembrane protein that known to be necessary for the long-term survival of nociceptive and autonomic ganglion neurons. Recent work has shown that FAM134B plays a pivotal role in autophagymediated turnover of ER membranes, tumor inhibition and lipid homeostasis. In this study, we provide mechanistic links between FAM134B and ARF-related protein 1 (ARFRP1) and further show that FAM134B resides in the Golgi apparatus. Here, we found that FAM134B increased lipid accumulation in adipocytes...
October 1, 2018: Biological Chemistry
Carlos R Ferreira, Zhi-Jie Xia, Aurélie Clément, David A Parry, Mariska Davids, Fulya Taylan, Prashant Sharma, Coleman T Turgeon, Bernardo Blanco-Sánchez, Bobby G Ng, Clare V Logan, Lynne A Wolfe, Benjamin D Solomon, Megan T Cho, Ganka Douglas, Daniel R Carvalho, Heiko Bratke, Marte Gjøl Haug, Jennifer B Phillips, Jeremy Wegner, Michael Tiemeyer, Kazuhiro Aoki, Ann Nordgren, Anna Hammarsjö, Angela L Duker, Luis Rohena, Hanne Buciek Hove, Jakob Ek, David Adams, Cynthia J Tifft, Tito Onyekweli, Tara Weixel, Ellen Macnamara, Kelly Radtke, Zöe Powis, Dawn Earl, Melissa Gabriel, Alvaro H Serrano Russi, Lauren Brick, Mariya Kozenko, Emma Tham, Kimiyo M Raymond, John A Phillips, George E Tiller, William G Wilson, Rizwan Hamid, May C V Malicdan, Gen Nishimura, Giedre Grigelioniene, Andrew Jackson, Monte Westerfield, Michael B Bober, William A Gahl, Hudson H Freeze
The conserved oligomeric Golgi (COG) complex is involved in intracellular vesicular transport, and is composed of eight subunits distributed in two lobes, lobe A (COG1-4) and lobe B (COG5-8). We describe fourteen individuals with Saul-Wilson syndrome, a rare form of primordial dwarfism with characteristic facial and radiographic features. All affected subjects harbored heterozygous de novo variants in COG4, giving rise to the same recurrent amino acid substitution (p.Gly516Arg). Affected individuals' fibroblasts, whose COG4 mRNA and protein were not decreased, exhibited delayed anterograde vesicular trafficking from the ER to the Golgi and accelerated retrograde vesicular recycling from the Golgi to the ER...
October 4, 2018: American Journal of Human Genetics
Koushik Das, Tomoyoshi Nozaki
Eukaryotic cells are organized into separate membrane-bound compartments that have specialized biochemical signature and function. Maintenance and regulation of distinct identity of each compartment is governed by the uneven distribution and intra-cellular movement of two essential biomolecules, lipids, and proteins. Non-vesicular lipid transport mediated by lipid transfer proteins plays a pivotal role in intra-cellular lipid trafficking and homeostasis whereas vesicular transport plays a central role in protein trafficking...
2018: Frontiers in Cellular and Infection Microbiology
Krishna Priya Thangaretnam, Oviya Sivam, Priya Ramanathan, Gopal Gopisetty, Thangarajan Rajkuma
BACKGROUND AND OBJECTIVE: CD99/MIC2gene product is a heavily glycosylated transmembrane protein which plays a major role in homotypic cell adhesion, apoptosis of double positive T cells and vesicular protein trafficking. It is over expressed in various cancers and has been considered as an ideal therapeutic target. The present study focused at developing monoclonal antibodies against the extracellular domain (ECD) of CD99 using hybridoma technology. MATERIALS AND METHODS: In order to generate monoclonal antibodies, the recombinant ECD of CD99 was used for immunizing the mice...
September 21, 2018: Human Antibodies
Kuldeep Verma, Vijay Kumar Srivastava, Sunando Datta
Rab GTPases constitute the largest subgroup in the Ras superfamily of GTPases. It is well established that different Rab GTPases are localized in discrete subcellular localization and regulate the membrane trafficking in nearly all eukaryotic cells. Rab GTPase diversity is often regarded as an expression of vesicular trafficking complexity. The pathogenic amoeba Entamoeba histolytica harbours 91 Rab GTPases which is the highest among the currently available genome sequences from the eukaryotic kingdom. Here, we review the current status of amoebic Rab GTPases diversity, unique biochemical and structural features and summarise their predicted regulators...
October 1, 2018: Small GTPases
Asuncion Carmona, Charles E Zogzas, Stephane Roudeau, Francesco Porcaro, Jan Garrevoet, Kathryn Spiers, Murielle Salome, Peter Cloetens, Somshuvra Mukhopadhyay, Richard Ortega
Manganese (Mn) is an essential metal that can be neurotoxic when elevated exposition occurs leading to parkinsonian-like syndromes. Mutations in the Slc30a10 gene have been identified in new forms of familial parkinsonism. SLC30A10 is a cell surface protein involved in the efflux of Mn protecting the cell against Mn toxicity. Disease causing mutations block the efflux activity of SLC30A10, resulting in Mn accumulation. Determining the intracellular localization of Mn when disease-causing SLC30A10 mutants are expressed is essential to elucidate the mechanisms of Mn neurotoxicity...
October 1, 2018: ACS Chemical Neuroscience
Gagandeep K Khurana, Poonam Vishwakarma, Niti Puri, Andrew Michael Lynn
Proteins of the SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptors) family play a significant role in all vesicular fusion events involved in endocytic and exocytic pathways. These proteins act as molecular machines that assemble into tight four-helix bundle complex, bridging the opposing membranes into close proximity forming membrane fusion. Almost all SNARE proteins share a 53 amino acid coiled-coil domain, which is mostly linked to the transmembrane domain at the C-terminal end...
2018: Bioinformation
Xian Zhang, Timothy Y Huang, Joel Yancey, Hong Luo, Yunwu Zhang
Alzheimer's disease (AD) comprises two major pathological hallmarks: extraneuronal deposition of β-amyloid (Aβ) peptides ("senile plaques") and intraneuronal aggregation of the microtubule-associated protein tau ("neurofibrillary tangles"). Aβ is derived from sequential cleavage of the β-amyloid precursor protein by β- and γ-secretases, while aggregated tau is hyperphosphorylated in AD. Mounting evidence suggests that dysregulated trafficking of these AD-related proteins contributes to AD pathogenesis...
September 27, 2018: ACS Chemical Neuroscience
Karina Ringer, Jana Riehl, Manuel Müller, Jenny Dewes, Florian Hoff, Ralf Jacob
A highly specific transport and sorting machinery directing secretory cargo to the apical or basolateral plasma membrane maintains the characteristic polarized architecture of epithelial cells. This machinery comprises a defined set of transport carriers, which are crucial for cargo delivery to the correct membrane domain. Each carrier is composed of a distinct set of proteins to verify precise routing and cargo selection. Among these components the dynamin-related GTPase Mx1 was identified on post-Golgi vesicles destined for the apical membrane of MDCK cells...
September 23, 2018: Traffic
Luis A Constantino-Jonapa, Verónica Ivonne Hernández-Ramírez, Carlos Osorio-Trujillo, Patricia Talamás-Rohana
Rab proteins are present in all eukaryotic lineages and regulate vesicular trafficking. Entamoeba histolytica has approximately 100 genes encoding Rab proteins, among which 16 have homology with human Rab proteins. Human Rab21 participates in integrin recycling, and thus amoebic Rab21 was believed to regulate the mobilization of Ehβ1FNR (integrin-like fibronectin receptor related with human integrin β1). We analyzed the distribution of EhRab21 using a polyclonal antibody produced with a specific peptide against the amoebic Rab protein, using confocal microscopy and specific probes for different organelles...
September 20, 2018: Microscopy Research and Technique
Giuseppina Grieco, Virginie Janssens, Héloïse P Gaide Chevronnay, Francisca N'Kuli, Patrick Van Der Smissen, Tongsong Wang, Jingdong Shan, Seppo Vainio, Benoit Bilanges, François Jouret, Bart Vanhaesebroeck, Christophe E Pierreux, Pierre J Courtoy
Kidney proximal tubular cells (PTCs) are highly specialized for ultrafiltrate reabsorption and serve as paradigm of apical epithelial differentiation. Vps34/PI3-kinase type III (PI3KC3) regulates endosomal dynamics, macroautophagy and lysosomal function. However, its in vivo role in PTCs has not been evaluated. Conditional deletion of Vps34/PI3KC3 in PTCs by Pax8-Cre resulted in early (P7) PTC dysfunction, manifested by Fanconi-like syndrome, followed by kidney failure (P14) and death. By confocal microscopy, Vps34∆/∆ PTCs showed preserved apico-basal specification (brush border, NHERF-1 versus Na+ /K+ -ATPase, ankyrin-G) but basal redistribution of late-endosomes/lysosomes (LAMP-1) and mis-localization to lysosomes of apical recycling endocytic receptors (megalin, cubilin) and apical non-recycling solute carriers (NaPi-IIa, SGLT-2)...
September 20, 2018: Scientific Reports
John S Ruano-Salguero, Kelvin H Lee
Representative in vitro blood-brain barrier (BBB) models can support the development of strategies to efficiently deliver therapeutic drugs to the brain by aiding the characterization of their internalization, trafficking, and subsequent transport across the BBB. A collagen type I (COL1) hydrogel-based in vitro BBB model was developed to enable the simultaneous characterization of drug transport and intracellular processing using confocal microscopy, in a way that traditional insert-based in vitro BBB models cannot...
October 1, 2018: Molecular Pharmaceutics
Matthias Munz, Gesa M Richter, Bruno G Loos, Søren Jepsen, Kimon Divaris, Steven Offenbacher, Alexander Teumer, Birte Holtfreter, Thomas Kocher, Corinna Bruckmann, Yvonne Jockel-Schneider, Christian Graetz, Loreto Munoz, Anita Bhandari, Stephanie Tennstedt, Ingmar Staufenbiel, Nathalie van der Velde, André G Uitterlinden, Lisette C P G M de Groot, Jürgen Wellmann, Klaus Berger, Bastian Krone, Per Hoffmann, Matthias Laudes, Wolfgang Lieb, Andre Franke, Henrik Dommisch, Jeanette Erdmann, Arne S Schaefer
Evidence for a shared genetic basis of association between coronary artery disease (CAD) and periodontitis (PD) exists. To explore the joint genetic basis, we performed a GWAS meta-analysis. In the discovery stage, we used a German aggressive periodontitis sample (AgP-Ger; 680 cases vs 3,973 controls) and the CARDIoGRAMplusC4D CAD meta-analysis dataset (60,801 cases vs 123,504 controls). Two SNPs at the known CAD risk loci ADAMTS7 (rs11634042) and VAMP8 (rs1561198) passed the pre-assigned selection criteria (PAgP-Ger  < 0...
September 12, 2018: Scientific Reports
Hammad Tashkandi, Afshin Shameli, Clifford V Harding, Robert W Maitta
Effects of α-synuclein deficiency on cellular blood components have not been extensively investigated. This study evaluated ultrastructural changes of leukocytes in α-synuclein knockout (KO) mice using electron microscopy (EM). The following ultrastructural characteristics were quantified in leukocytes: mitochondria, primary granules, specific granules (SG), Golgi apparatus (GA), inclusions, rough-endoplasmic reticulum (RER), smooth-endoplasmic reticulum (SER), and cellular projections (CP). EM showed increased numbers or amounts of SG, inclusions, and SER in KO group (5...
November 2018: Blood Cells, Molecules & Diseases
Shuwei Xie, James B Reinecke, Trey Farmer, Kriti Bahl, Ivana Yeow, Benjamin J Nichols, Tiffany A McLamarrah, Naava Naslavsky, Gregory C Rogers, Steve Caplan
Centrosomes are the major microtubule-nucleating and organizing centers of cells and play crucial roles in microtubule anchoring, organelle positioning, and cilliogenesis. At the centrosome core lies a tightly-associated or 'engaged' mother-daughter centriole pair.  During mitotic exit, removal of centrosomal proteins pericentrin and Cep215 promotes 'disengagement' by the dissolution of inter-centriolar linkers, ensuring a single centriole duplication event per cell cycle.  Herein, we explore a new mechanism involving vesicular trafficking for the removal of centrosomal Cep215...
September 6, 2018: Molecular Biology of the Cell
Michèle Roy, Sophie Roux
Osteoclasts (OCs) are bone-resorbing cells that maintain bone homeostasis. OC differentiation, survival, and activity are regulated by numerous small GTPases, including those of the Rab family, which are involved in plasma membrane delivery and lysosomal and autophagic degradation pathways. In resorbing OCs, polarized vesicular trafficking pathways also result in formation of the ruffled membrane, the resorbing organelle, and in transcytosis.
2018: BioMed Research International
Hiroyuki Morita, Akihito Matsuoka, Jun-Ichiro Kida, Hiroyuki Tabata, Kaoru Tohyama, Yumi Tohyama
A microtubule-associated motor protein, kinesin-like family member 20A (KIF20A; also called MKlp2) is required for cytokinesis and contributes to intracellular vesicular trafficking. KIF20A plays a critical role in the development of several cancers, but its role in blood cells and hematological malignancies have not been studied. In the present study, we focused on the role of KIF20A in hematopoietic cells and possible involvement in myeloid neoplasms. We found that human leukemia cell lines and normal bone marrow CD34-positive cells stimulated by growth factors, but not mature peripheral blood cells, exhibit high KIF20A expression...
September 4, 2018: International Journal of Hematology
Jin-Zheng Wang, Katayoon Dehesh
Cellular adaptive responses arise from an array of spatially and temporally distinct biochemical interactions that modulate biological processes and reorganize subcellular structures tailored to the nature of stimulus. As such, cells have evolved elegantly and tightly regulated mechanisms to enable interorganellar communication in part through the dynamic readjustment of physical distance enabling the tethering between two closely apposed membranous organelles and thus formation of Membrane Contact Sites (MCSs)...
August 24, 2018: Current Opinion in Plant Biology
Angel Stanoev, Amit Mhamane, Klaus C Schuermann, Hernán E Grecco, Wayne Stallaert, Martin Baumdick, Yannick Brüggemann, Maitreyi S Joshi, Pedro Roda-Navarro, Sven Fengler, Rabea Stockert, Lisaweta Roßmannek, Jutta Luig, Aneta Koseska, Philippe I H Bastiaens
The proto-oncogenic epidermal growth factor receptor (EGFR) is a tyrosine kinase whose sensitivity to growth factors and signal duration determines cellular behavior. We resolve how EGFR's response to epidermal growth factor (EGF) originates from dynamically established recursive interactions with spatially organized protein tyrosine phosphatases (PTPs). Reciprocal genetic PTP perturbations enabled identification of receptor-like PTPRG/J at the plasma membrane and ER-associated PTPN2 as the major EGFR dephosphorylating activities...
September 26, 2018: Cell Systems
Rohan Sharma, Ravinder Gulia, Samarjit Bhattacharyya
Group I metabotropic glutamate receptors (mGluRs) function as modulators of neuronal physiology and they have also been implicated in various neuropsychiatric disorders. Trafficking of mGluRs plays important roles in controlling the precise localization of these receptors at specific region of the cell, as well as it regulates the activity of these receptors. Despite this obvious significance, we know very little about the cellular machineries that control the trafficking of these receptors in the CNS. Sorting nexin 1 (SNX1) has been shown to regulate the endosomal sorting of few cell surface receptors either to lysosomes where they are downregulated or back to the cell surface...
October 3, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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