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https://www.readbyqxmd.com/read/28428220/cmtm3-cklf-like-marvel-transmembrane-domain-3-mediates-angiogenesis-by-regulating-cell-surface-availability-of-ve-cadherin-in-endothelial-adherens-junctions
#1
Ihsan Chrifi, Laura Louzao-Martinez, Maarten Brandt, Christian G M van Dijk, Petra Burgisser, Changbin Zhu, Johan M Kros, Dirk J Duncker, Caroline Cheng
OBJECTIVE: Decrease in VE-cadherin adherens junctions reduces vascular stability, whereas disruption of adherens junctions is a requirement for neovessel sprouting during angiogenesis. Endocytosis plays a key role in regulating junctional strength by altering bioavailability of cell surface proteins, including VE-cadherin. Identification of new mediators of endothelial endocytosis could enhance our understanding of angiogenesis. Here, we assessed the function of CMTM3 (CKLF-like MARVEL transmembrane domain 3), which we have previously identified as highly expressed in Flk1(+) endothelial progenitor cells during embryonic development...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28408870/homeostatic-changes-in-gaba-and-glutamate-receptors-on-excitatory-cortical-neurons-during-sleep-deprivation-and-recovery
#2
Esther Del Cid-Pellitero, Anton Plavski, Lynda Mainville, Barbara E Jones
Neuronal activity is regulated in a homeostatic manner through changes in inhibitory GABA and excitatory glutamate (Glu) AMPA (A) receptors (GluARs). Using immunofluorescent staining, we examined whether calcium/calmodulin-dependent protein kinase IIα (CaMKIIα)-labeled (+) excitatory neurons in the barrel cortex undergo such homeostatic regulation following enforced waking with associated cortical activation during the day when mice normally sleep the majority of the time. Sleep deprived mice were prevented from falling asleep by unilateral whisker stimulation and sleep recovery (SR) mice allowed to sleep freely following deprivation...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28407399/abnormal-rab11-rab8-vesicles-cluster-in-enterocytes-of-patients-with-microvillus-inclusion-disease
#3
Georg F Vogel, Andreas R Janecke, Iris M Krainer, Karin Gutleben, Barbara Witting, Sally G Mitton, Sahar Mansour, Antje Ballauff, Joseph T Roland, Amy C Engevik, Ernest Cutz, Thomas Müller, James R Goldenring, Lukas A Huber, Michael W Hess
Microvillus Inclusion Disease (MVID) is a congenital enteropathy characterized by accumulation of vesiculo-tubular endomembranes in the subapical cytoplasm of enterocytes, historically termed "secretory granules". However, neither their identity nor pathophysiological significance is well defined. Using immunoelectron microscopy and tomography we studied biopsies from MVID patients (3x Myosin 5b mutations, 1x Syntaxin3 mutation) and compared them to controls and genome-edited CaCo2 cell models, harboring relevant mutations...
April 13, 2017: Traffic
https://www.readbyqxmd.com/read/28396819/rab11-fip1-phosphorylation-by-mark2-regulates-polarity-in-mdck-cells
#4
Rebecca McRae, Lynne A Lapierre, Elizabeth H Manning, James R Goldenring
MARK2/Par1b/EMK1, a serine/threonine kinase, is required for correct apical/basolateral membrane polarization in epithelial cells. However, the specific substrates mediating MARK2 action are less well understood. We have now found that MARK2 phosphorylates Rab11-FIP1B/C at serine 234 in a consensus site similar to that previously identified in Rab11-FIP2. In MDCK cells undergoing repolarization after a calcium switch, antibodies specific for pS234-Rab11-FIP1 or pS227-Rab11-FIP2 demonstrate that the spatial and temporal activation of Rab11-FIP1 phosphorylation is distinct from that for Rab11-FIP2...
2017: Cellular Logistics
https://www.readbyqxmd.com/read/28396666/dynamic-changes-in-the-intracellular-association-of-selected-rab-small-gtpases-with-mhc-class-ii-and-dm-during-dendritic-cell-maturation
#5
Gibrán Pérez-Montesinos, Orestes López-Ortega, Jessica Piedra-Reyes, Laura C Bonifaz, José Moreno
Antigen processing for presentation by major histocompatibility complex class II (MHCII) molecules requires the latter to travel through the endocytic pathway together with its chaperons: the invariant chain (Ii) and DM. Nevertheless, the nature of the compartments where MHCII molecules travel to acquire peptides lacks definition regarding molecules involved in intracellular vesicular trafficking, such as Rab small GTPases. We aimed to define which Rab proteins are present during the intracellular transport of MHCII, DM, and Ii through the endocytic pathway on their route to the cell surface during dendritic cell (DC) maturation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28394692/exploring-the-iceberg-prospects-of-coordinated-myosin-v-and-actin-assembly-functions-in-transport-processes
#6
Tobias Welz, Eugen Kerkhoff
Spir actin nucleators and myosin V motor proteins were recently discovered to coexist in a protein complex. The direct interaction allows the coordinated activation of actin motor proteins and actin filament track generation at vesicle membranes. By now the cooperation of myosin V (MyoV) motors and Spir actin nucleation function has only been shown in the exocytic transport of Rab11 vesicles in metaphase mouse oocytes. Next to Rab11, myosin V motors however interact with a variety of Rab GTPases including Rab3, Rab8 and Rab10...
April 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28384198/tbc1d12-is-a-novel-rab11-binding-protein-that-modulates-neurite-outgrowth-of-pc12-cells
#7
Mai E Oguchi, Kenta Noguchi, Mitsunori Fukuda
Recycling endosomes are generally thought to play a central role in endocytic recycling, but recent evidence has indicated that they also participate in other cellular events, including cytokinesis, autophagy, and neurite outgrowth. Rab small GTPases are key regulators in membrane trafficking, and although several Rab isoforms, e.g., Rab11, have been shown to regulate recycling endosomal trafficking, the precise mechanism by which these Rabs regulate recycling endosomes is not fully understood. In this study, we focused on a Rab-GTPase-activating protein (Rab-GAP), one of the key regulators of Rabs, and comprehensively screened 43 mammalian Tre-2/Bub2/Cdc16 (TBC)/Rab-GAP-domain-containing proteins (TBC proteins) for proteins that specifically localize on recycling endosomes in mouse embryonic fibroblasts (MEFs)...
2017: PloS One
https://www.readbyqxmd.com/read/28381422/polo-kinase-mediates-the-phosphorylation-and-cellular-localization-of-nuf-fip3-a-rab11-effector
#8
Lotti Brose, Justin Crest, Li Tao, William Sullivan
Animal cytokinesis involves both actin-myosin based contraction and vesicle-mediated membrane addition. In many cell types, including early Drosophila embryos, Nuf/FIP3, a Rab11 effector, mediates recycling endosome (RE)-based vesicle delivery to the cytokinesis furrow. Nuf exhibits a cell cycle-regulated concentration at the centrosome that is accompanied by dramatic changes in its phosphorylation state. Here we demonstrate maximal phosphorylation of Nuf occurs at prophase, when centrosome-associated Nuf disperses throughout the cytoplasm...
April 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28352128/recruitment-of-lyn-from-endomembranes-to-the-plasma-membrane-through-calcium-dependent-cell-cell-interactions-upon-polarization-of-inducible-lyn-expressing-mdck-cells
#9
Takao Morinaga, Sayuri Yanase, Aya Okamoto, Noritaka Yamaguchi, Naoto Yamaguchi
Src-family kinases, expressed in a wide variety of cell types, are anchored to cellular membranes through posttranslational lipid modifications and involved in diverse cellular signalling. In epithelial cells, Src-family kinases are localized at the plasma membrane and participate in epithelial functions. Epithelial cell polarity is achieved through dynamic reorganization of protein trafficking. To examine the trafficking of Src-family kinases between polarized and non-polarized epithelial cells, we generated an MDCK cell line that can inducibly express a protein of interest in a polarized state at any time...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28348980/overexpression-of-the-endosomal-anion-proton-exchanger-clc-5-increases-cell-susceptibility-toward-clostridium-difficile-toxins-tcda-and-tcdb
#10
Frederike Ruhe, Alexandra Olling, Rasmus Abromeit, Dennis Rataj, Matthias Grieschat, Andre Zeug, Ralf Gerhard, Alexi Alekov
Virulent C. difficile toxins TcdA and TcdB invade host intestinal epithelia by endocytosis and use the acidic environment of intracellular vesicles for further processing and activation. We investigated the role of ClC-5, a chloride/proton exchanger expressed in the endosomes of gastrointestinal epithelial cells, in the activation and processing of C. difficile toxins. Enhanced intoxication by TcdA and TcdB was observed in cells expressing ClC-5 but not ClC-4, another chloride/proton exchanger with similar function but different localization...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28334871/proteomics-insights-into-infantile-neuronal-ceroid-lipofuscinosis-cln1-point-to-the-involvement-of-cilia-pathology-in-the-disease
#11
Michal Segal-Salto, Karin Hansson, Tamar Sapir, Anna Kaplan, Talia Levy, Michaela Schwizer, Michael Frotscher, Peter James, Orly Reiner
Mutations in the depalmitoylation enzyme, palmitoyl protein thioesterase (PPT1), result in the early onset neurodegenerative disease known as Infantile Neuronal Ceroid Lipofuscinosis. Here, we provide proteomic evidence suggesting that PPT1 deficiency could be considered as a ciliopathy. Analysis of membrane proteins from brain enriched for acylated proteins from neonate Ppt1 knock out and control mice revealed a list of 88 proteins with differential expression levels. Amongst them, we identified Rab3IP, which regulates ciliogenesis in concert with Rab8 and Rab11...
March 6, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28303263/astrocyte-ca-2-influx-negatively-regulates-neuronal-activity
#12
Yao V Zhang, Kiel G Ormerod, J Troy Littleton
Maintenance of neural circuit activity requires appropriate regulation of excitatory and inhibitory synaptic transmission. Recently, glia have emerged as key partners in the modulation of neuronal excitability; however, the mechanisms by which glia regulate neuronal signaling are still being elucidated. Here, we describe an analysis of how Ca(2+) signals within Drosophila astrocyte-like glia regulate excitability in the nervous system. We find that Drosophila astrocytes exhibit robust Ca(2+) oscillatory activity manifested by fast, recurrent microdomain Ca(2+) fluctuations within processes that infiltrate the synaptic neuropil...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28294115/phosphorylation-of-rab-coupling-protein-by-lmtk3-controls-rab14-dependent-epha2-trafficking-to-promote-cell-cell-repulsion
#13
Christine Gundry, Sergi Marco, Elena Rainero, Bryan Miller, Emmanuel Dornier, Louise Mitchell, Patrick T Caswell, Andrew D Campbell, Anna Hogeweg, Owen J Sansom, Jennifer P Morton, Jim C Norman
The Rab GTPase effector, Rab-coupling protein (RCP) is known to promote invasive behaviour in vitro by controlling integrin and receptor tyrosine kinase (RTK) trafficking, but how RCP influences metastasis in vivo is unclear. Here we identify an RTK of the Eph family, EphA2, to be a cargo of an RCP-regulated endocytic pathway which controls cell:cell repulsion and metastasis in vivo. Phosphorylation of RCP at Ser(435) by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser(897) by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart...
March 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28251922/early-stages-of-functional-diversification-in-the-rab-gtpase-gene-family-revealed-by-genomic-and-localization-studies-in-paramecium-species
#14
Lydia J Bright, Jean-Francois Gout, Michael Lynch
New gene functions arise within existing gene families as a result of gene duplication and subsequent diversification. To gain insight into the steps that led to the functional diversification of paralogues, we tracked duplicate retention patterns, expression-level divergence, and subcellular markers of functional diversification in the Rab GTPase gene family in three Paramecium aurelia species. After whole-genome duplication, Rab GTPase duplicates are more highly retained than other genes in the genome but appear to be diverging more rapidly in expression levels, consistent with early steps in functional diversification...
April 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28235896/pathogenic-huntington-alters-bmp-signaling-and-synaptic-growth-through-local-disruptions-of-endosomal-compartments
#15
Yulia Akbergenova, J Troy Littleton
Huntington's disease (HD) is a neurodegenerative disorder caused by expansion of a polyglutamine (polyQ) stretch within the Huntingtin (Htt) protein. Pathogenic Htt disrupts multiple neuronal processes, including gene expression, axonal trafficking, proteasome and mitochondrial activity, and intracellular vesicle trafficking. However, the primary pathogenic mechanism and subcellular site of action for mutant Htt are still unclear. Using a Drosophila HD model, we found that pathogenic Htt expression leads to a profound overgrowth of synaptic connections that correlates directly with the levels of Htt at nerve terminals...
March 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28235866/rab11-fip3-regulation-of-lck-endosomal-traffic-controls-tcr-signal-transduction
#16
Jérôme Bouchet, Iratxe Del Río-Iñiguez, Elena Vázquez-Chávez, Rémi Lasserre, Sonia Agüera-González, Céline Cuche, Mary W McCaffrey, Vincenzo Di Bartolo, Andrés Alcover
The role of endosomes in receptor signal transduction is a long-standing question, which remains largely unanswered. The T cell Ag receptor and various components of its proximal signaling machinery are associated with distinct endosomal compartments, but how endosomal traffic affects T cell signaling remains ill-defined. In this article, we demonstrate in human T cells that the subcellular localization and function of the protein tyrosine kinase Lck depends on the Rab11 effector FIP3 (Rab11 family interacting protein-3)...
February 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28228550/interaction-of-phosphorylated-rab11-fip2-with-eps15-regulates-apical-junction-composition
#17
Lynne A Lapierre, Elizabeth H Manning, Kenya M Mitchell, Cathy M Caldwell, James R Goldenring
MARK2 regulates the establishment of polarity in Madin-Darby canine kidney (MDCK) cells in part through phosphorylation of serine 227 of Rab11-FIP2. We identified Eps15 as an interacting partner of phospho-S227-Rab11-FIP2 (pS227-FIP2). During recovery from low calcium, Eps15 localized to the lateral membrane before pS227-FIP2 arrival. Later in recovery, Eps15 and pS227-FIP2 colocalized at the lateral membrane. In MDCK cells expressing the pseudophosphorylated FIP2 mutant FIP2(S227E), during recovery from low calcium, Eps15 was trapped and never localized to the lateral membrane...
April 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28225130/systematic-investigation-on-the-intracellular-trafficking-network-of-polymeric-nanoparticles
#18
Jinxie Zhang, Danfeng Chang, Yao Yang, Xudong Zhang, Wei Tao, Lijuan Jiang, Xin Liang, Hsiangi Tsai, Laiqiang Huang, Lin Mei
Polymeric nanoparticles such as PLGA-based nanoparticles are emerging as promising carriers for controlled drug delivery. However, little is known about the intracellular trafficking network of polymeric nanoparticles. Here, more than 30 Rab proteins were used as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy to investigate in detail the intracellular trafficking pathways of PLGA nanoparticles. We observed that coumarin-6-loaded PLGA nanoparticles were internalized by the cells mainly through caveolin and clathrin-dependent endocytosis and Rab34-mediated macropinocytosis...
February 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28209731/transport-of-fungal-rab11-secretory-vesicles-involves-myosin-5-dynein-dynactin-p25-and-kinesin-1-and-is-independent-of-kinesin-3
#19
Miguel A Peñalva, Jun Zhang, Xin Xiang, Areti Pantazopoulou
Hyphal tip cells of the fungus Aspergillus nidulans are useful for studying long-range intracellular traffic. Post-Golgi secretory vesicles (SVs) containing the RAB11 orthologue RabE engage myosin-5 as well as plus end- and minus end-directed microtubule motors, providing an experimental system with which to investigate the interplay between microtubule and actin motors acting on the same cargo. By exploiting the fact that depolymerization of F-actin unleashes SVs focused at the apex by myosin-5 to microtubule-dependent motors, we establish that the minus end-directed transport of SVs requires the dynein/dynactin supercomplex...
April 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28180992/comprehensive-functional-analysis-of-rab-gtpases-in-drosophila-nephrocytes
#20
Yulong Fu, Jun-Yi Zhu, Fujian Zhang, Adam Richman, Zhanzheng Zhao, Zhe Han
The Drosophila nephrocyte is a critical component of the fly renal system and bears structural and functional homology to podocytes and proximal tubule cells of the mammalian kidney. Investigations of nephrocyte cell biological processes are fundamental to understanding the insect renal system. Nephrocytes are highly active in endocytosis and vesicle trafficking. Rab GTPases regulate endocytosis and trafficking but specific functions of nephrocyte Rabs remain undefined. We analyzed Rab GTPase expression and function in Drosophila nephrocytes and found that 11 out of 27 Drosophila Rabs were required for normal activity...
February 8, 2017: Cell and Tissue Research
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