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Rab4 Endosomes

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https://www.readbyqxmd.com/read/30097810/cmtm4-regulates-angiogenesis-by-promoting-cell-surface-recycling-of-ve-cadherin-to-endothelial-adherens-junctions
#1
Ihsan Chrifi, Laura Louzao-Martinez, Maarten M Brandt, Christian G M van Dijk, Petra E Bürgisser, Changbin Zhu, Johan M Kros, Marianne C Verhaar, Dirk J Duncker, Caroline Cheng
Vascular endothelial (VE) cadherin is a key component of endothelial adherens junctions (AJs) and plays an important role in maintaining vascular integrity. Endocytosis of VE-cadherin regulates junctional strength and a decrease of surface VE-cadherin reduces vascular stability. However, disruption of AJs is also a requirement for vascular sprouting. Identifying novel regulators of endothelial endocytosis could enhance our understanding of angiogenesis. Here, we evaluated the angiogenic potential of (CKLF-like MARVEL transmembrane domain 4) CMTM4 and assessed in which molecular pathway CMTM4 is involved during angiogenesis...
August 10, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29958948/wip-itsn1-complex-is-involved-in-cellular-vesicle-trafficking-and-formation-of-filopodia-like-protrusions
#2
Tetyana Gryaznova, Olga Gubar, Mariia Burdyniuk, Sergii Kropyvko, Alla Rynditch
WIP (WASP interacting protein) together with N-WASP (neural Wiskott-Aldrich syndrome protein) regulates actin polymerization that is crucial for invadopodia and filopodia formation. Recently, we reported the WIP interaction with ITSN1 which is highly implicated in endo-/exocytosis, apoptosis, mitogenic signaling and cytoskeleton rearrangements. Here we demonstrate that the WIP/ITSN1 complex is involved in the transferrin receptor recycling and partially co-localizes with a marker of the fast recycling endosomes, RAB4...
October 20, 2018: Gene
https://www.readbyqxmd.com/read/29847800/neurobeachin-and-the-kinesin-kif21b-are-critical-for-endocytic-recycling-of-nmda-receptors-and-regulate-social-behavior
#3
Kira V Gromova, Mary Muhia, Nicola Rothammer, Christine E Gee, Edda Thies, Irina Schaefer, Sabrina Kress, Manfred W Kilimann, Olga Shevchuk, Thomas G Oertner, Matthias Kneussel
Autism spectrum disorders (ASDs) are associated with mutations affecting synaptic components, including GluN2B-NMDA receptors (NMDARs) and neurobeachin (NBEA). NBEA participates in biosynthetic pathways to regulate synapse receptor targeting, synaptic function, cognition, and social behavior. However, the role of NBEA-mediated transport in specific trafficking routes is unclear. Here, we highlight an additional function for NBEA in the local delivery and surface re-insertion of synaptic receptors in mouse neurons...
May 29, 2018: Cell Reports
https://www.readbyqxmd.com/read/29476049/vps3-and-vps8-control-integrin-trafficking-from-early-to-recycling-endosomes-and-regulate-integrin-dependent-functions
#4
C T H Jonker, R Galmes, T Veenendaal, C Ten Brink, R E N van der Welle, N Liv, J de Rooij, A A Peden, P van der Sluijs, C Margadant, J Klumperman
Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis. Yet, the molecular machineries that drive endocytic recycling remain largely unclear. The CORVET complex is a multi-subunit tether required for fusion between early endosomes. Here we show that the CORVET-specific subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes. Vps3 and Vps8 localise to Rab4-positive recycling vesicles and co-localise with the CHEVI complex on Rab11-positive recycling endosomes...
February 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29425100/the-rab-effector-protein-rabep2-regulates-endosomal-trafficking-to-mediate-vascular-endothelial-growth-factor-receptor-2-vegfr2-dependent-signaling
#5
Natalie Kofler, Federico Corti, Felix Rivera-Molina, Yong Deng, Derek Toomre, Michael Simons
As a master regulator of endothelial cell function, vascular endothelial growth factor receptor-2 (VEGFR2) activates multiple downstream signaling pathways that are critical for vascular development and normal vessel function. VEGFR2 trafficking through various endosomal compartments modulates its signaling output. Accordingly, proteins that regulate the speed and direction by which VEGFR2 traffics through endosomes have been demonstrated to be particularly important for arteriogenesis. However, little is known about how these proteins control VEGFR2 trafficking and about the implications of this control for endothelial cell function...
March 30, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29065163/drosophila-vamp7-regulates-wingless-intracellular-trafficking
#6
Han Gao, Fang He, Xinhua Lin, Yihui Wu
Drosophila Wingless (Wg) is a morphogen that determines cell fate during development. Previous studies have shown that endocytic pathways regulate Wg trafficking and signaling. Here, we showed that loss of vamp7, a gene required for vesicle fusion, dramatically increased Wg levels and decreased Wg signaling. Interestingly, we found that levels of Dally-like (Dlp), a glypican that can interact with Wg to suppress Wg signaling at the dorsoventral boundary of the Drosophila wing, were also increased in vamp7 mutant cells...
2017: PloS One
https://www.readbyqxmd.com/read/28954865/retromer-stops-beta-arrestin-1-mediated-signaling-from-internalized-cannabinoid-2-receptors
#7
Carlos Nogueras-Ortiz, Cristina Roman-Vendrell, Gabriel E Mateo-Semidey, Yu-Hsien Liao, Debra A Kendall, Guillermo A Yudowski
G protein-coupled receptors mediate their complex functions through activation of signaling cascades from receptors localized at the cell surface and endosomal compartments. These signaling pathways are modulated by heterotrimeric G proteins and the scaffold proteins beta-arrestin 1 and 2. However, in contrast to the events occurring at the cell surface, our knowledge of the mechanisms controlling signaling from receptors localized at intracellular compartments is still very limited. Here we sought to investigate the intracellular signaling from cannabinoid 2 receptor (CB2 R)...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28902870/reduced-insulin-signaling-maintains-electrical-transmission-in-a-neural-circuit-in-aging-flies
#8
Hrvoje Augustin, Kieran McGourty, Marcus J Allen, Sirisha Kudumala Madem, Jennifer Adcott, Fiona Kerr, Chi Tung Wong, Alec Vincent, Tanja Godenschwege, Emmanuel Boucrot, Linda Partridge
Lowered insulin/insulin-like growth factor (IGF) signaling (IIS) can extend healthy lifespan in worms, flies, and mice, but it can also have adverse effects (the "insulin paradox"). Chronic, moderately lowered IIS rescues age-related decline in neurotransmission through the Drosophila giant fiber system (GFS), a simple escape response neuronal circuit, by increasing targeting of the gap junctional protein innexin shaking-B to gap junctions (GJs). Endosomal recycling of GJs was also stimulated in cultured human cells when IIS was reduced...
September 2017: PLoS Biology
https://www.readbyqxmd.com/read/28822075/recycling-endosomes-in-human-cytotoxic-t-lymphocytes-constitute-an-auxiliary-intracellular-trafficking-pathway-for-newly-synthesized-perforin
#9
Kelsey Lesteberg, Jordan Orange, George Makedonas
Although cytotoxic T lymphocytes (CTLs) store perforin within cytoplasmic secretory granules for immediate use, perforin is synthesized anew within hours of TCR stimulation. Previously, we observed new perforin protein at an immunologic synapse independent of secretory lysosomes; herein, we aimed to determine how new perforin transits to the synapse if not via lytic granules. We analyzed antigen-specific human CTLs via imaging flow cytometry and high-resolution confocal microscopy, with attention to intracellular trafficking components and new perforin...
October 2017: Immunologic Research
https://www.readbyqxmd.com/read/28787457/acquisition-of-rab11-and-rab11-fip2-a-novel-strategy-for-chlamydia-pneumoniae-early-survival
#10
Katja Mölleken, Johannes H Hegemann
The initial steps in chlamydial infection involve adhesion and internalization into host cells and, most importantly, modification of the nascent inclusion to establish the intracellular niche. Here, we show that Chlamydia pneumoniae enters host cells via EGFR-dependent endocytosis into an early endosome with a phosphatidylinositol 3-phosphate (PI3P) membrane identity. Immediately after entry, the early chlamydial inclusion acquires early endosomal Rab GTPases including Rab4, Rab5, Rab7, as well as the two recycling-specific Rabs Rab11 and Rab14...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28604748/isoprenylcysteine-carboxylmethyltransferase-function-is-essential-for-rab4a-mediated-integrin-%C3%AE-3-recycling-cell-migration-and-cancer-metastasis
#11
M T Do, T F Chai, P J Casey, M Wang
Isoprenylcysteine carboxylmethyltransferase (ICMT) catalyzes the post-translational modification of RAB GTPases that contain C-terminal CXC motifs. However, the functional impact of this modification on RAB proteins has not been actively explored. We found that inhibition of ICMT significantly reduced cell migration in vitro and cancer invasion and metastasis in vivo. This role of ICMT was found to be mediated by RAB4A, an essential regulator of the fast recycling of integrin β3. Integrin β3 regulates cell polarity and migration when localized appropriately to the plasma membrane, thereby having an essential role in cancer metastasis...
October 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28273459/anterograde-transport-of-rab4-associated-vesicles-regulates-synapse-organization-in-drosophila
#12
Swagata Dey, Gary Banker, Krishanu Ray
Local endosomal recycling at synapses is essential to maintain neurotransmission. Rab4GTPase, found on sorting endosomes, is proposed to balance the flow of vesicles among endocytic, recycling, and degradative pathways in the presynaptic compartment. Here, we report that Rab4-associated vesicles move bidirectionally in Drosophila axons but with an anterograde bias, resulting in their moderate enrichment at the synaptic region of the larval ventral ganglion. Results from FK506 binding protein (FKBP) and FKBP-Rapamycin binding domain (FRB) conjugation assays in rat embryonic fibroblasts together with genetic analyses in Drosophila indicate that an association with Kinesin-2 (mediated by the tail domain of Kinesin-2α/KIF3A/KLP64D subunit) moves Rab4-associated vesicles toward the synapse...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28225130/systematic-investigation-on-the-intracellular-trafficking-network-of-polymeric-nanoparticles
#13
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...
March 2, 2017: Nanoscale
https://www.readbyqxmd.com/read/28191740/insulin-dependent-cytoplasmic-distribution-of-rab4a-in-mouse-adipocytes-is-inhibited-by-interleukin-6-8-and-15
#14
Maciej Błaszczyk, Małgorzata Gajewska, Marta Milewska, Katarzyna Grzelkowska-Kowalczyk
The purpose of the study was to examine the effect of interleukins, IL-6, IL-8, and IL-15, on insulin-mediated redistribution of Rab4a, an early endosome marker, in mouse 3T3-L1 adipocytes. The interleukins did not affect cell viability; however, cell number was slightly but significantly higher in cultures exposed to IL-8 and IL-15. IL-8 and IL-15 decreased lipid storage in adipocytes, whereas IL-6 had no effect. Rab4A showed cytoplasmic localization, and in control unstimulated adipocytes it was found primarily nearby nucleus, that was supported by cellular fluorescence distribution profile, and by calculated indices, that is, high percentage of near-nuclear area fluorescence and a low mean peripheral cytoplasmic fluorescence/mean near-nuclear fluorescence ratio...
April 2017: Cell Biology International
https://www.readbyqxmd.com/read/28031320/tetraspanin-cd63-controls-basolateral-sorting-of-organic-cation-transporter-2-in-renal-proximal-tubules
#15
Ulf Schulze, Sabine Brast, Alexander Grabner, Christian Albiker, Beatrice Snieder, Svenja Holle, Eberhard Schlatter, Rita Schröter, Hermann Pavenstädt, Edwin Herrmann, Carsten Lambert, Gilles A Spoden, Luise Florin, Paul Saftig, Giuliano Ciarimboli
CD63 is a ubiquitously expressed member of the tetraspanin superfamily. Using a mating-based split-ubiquitin-yeast 2-hybrid system, pull-down experiments, total internal reflection fluorescence microscopy, Förster resonance energy transfer, and biotinylation assays, we found that CD63 interacts with human organic cation transporter 2 (hOCT2), which transports endogenous and exogenous substrates, such as neurotransmitters and drugs in several epithelial cells. CD63 overexpression affects cellular localization of hOCT2 expressed in human embryonic kidney (HEK)293 cells...
April 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27852225/a-functional-endosomal-pathway-is-necessary-for-lysosome-biogenesis-in-drosophila
#16
Anne-Claire Jacomin, Marie-Odile Fauvarque, Emmanuel Taillebourg
BACKGROUND: Lysosomes are the major catabolic compartment within eukaryotic cells, and their biogenesis requires the integration of the biosynthetic and endosomal pathways. Endocytosis and autophagy are the primary inputs of the lysosomal degradation pathway. Endocytosis is specifically needed for the degradation of membrane proteins whereas autophagy is responsible for the degradation of cytoplasmic components. We previously identified the deubiquitinating enzyme UBPY/USP8 as being necessary for lysosomal biogenesis and productive autophagy in Drosophila...
November 16, 2016: BMC Cell Biology
https://www.readbyqxmd.com/read/27773542/hiv-nef-and-notch1-dependent-endocytosis-of-adam17-induces-vesicular-tnf-secretion-in-chronic-hiv-infection
#17
Christian Ostalecki, Sebastian Wittki, Jung-Hyun Lee, Miriam M Geist, Nadine Tibroni, Thomas Harrer, Gerold Schuler, Oliver T Fackler, Andreas S Baur
Tumor necrosis factor (TNF) is a key cytokine in HIV replication and pathogenesis. For reasons that are not entirely clear, the cytokine remains upregulated despite anti-retroviral therapy (ART). Here we demonstrate that HIV Nef induces an alternative TNF secretion mechanism that remains active in chronic infection. Ingestion of Nef-containing plasma extracellular vesicles (pEV) from ART patients by primary immune cells, but also Nef expression, induced intracellular proTNF cleavage and secretion of vesicular TNF endosomes...
November 2016: EBioMedicine
https://www.readbyqxmd.com/read/27627840/integrin-linked-kinase-and-elmo2-modulate-recycling-endosomes-in-keratinocytes
#18
Ernest Ho, Iordanka A Ivanova, Lina Dagnino
The formation of tight cell-cell junctions is essential in the epidermis for its barrier properties. In this tissue, keratinocytes follow a differentiation program tightly associated with their movement from the innermost basal to the outer suprabasal layers, and with changes in their cell-cell adhesion profile. Intercellular adhesion in keratinocytes is mediated through cell-cell contacts, including E-cadherin-based adherens junctions. Although the mechanisms that mediate E-cadherin delivery to the plasma membrane have been widely studied in simple epithelia, this process is less well understood in the stratified epidermis...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27412703/plasma-membrane-cholesterol-level-and-agonist-induced-internalization-of-%C3%AE-opioid-receptors-colocalization-study-with-intracellular-membrane-markers-of-rab-family
#19
Jana Brejchova, Miroslava Vosahlikova, Lenka Roubalova, Marco Parenti, Mario Mauri, Oleksandr Chernyavskiy, Petr Svoboda
Decrease of cholesterol level in plasma membrane of living HEK293 cells transiently expressing FLAG-δ-OR by β-cyclodextrin (β-CDX) resulted in a slight internalization of δ-OR. Massive internalization of δ-OR induced by specific agonist DADLE was diminished in cholesterol-depleted cells. These results suggest that agonist-induced internalization of δ-OR, which has been traditionally attributed exclusively to clathrin-mediated pathway, proceeds at least partially via membrane domains. Identification of internalized pools of FLAG-δ-OR by colocalization studies with proteins of Rab family indicated the decreased presence of receptors in early endosomes (Rab5), late endosomes and lysosomes (Rab7) and fast recycling vesicles (Rab4)...
August 2016: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/27235428/anaplasma-marginale-actively-modulates-vacuolar-maturation-during-intracellular-infection-of-its-tick-vector-dermacentor-andersoni
#20
Forgivemore Magunda, Chelsea Wright Thompson, David A Schneider, Susan M Noh
UNLABELLED: Tick-borne transmission of bacterial pathogens in the order Rickettsiales is responsible for diverse infectious diseases, many of them severe, in humans and animals. Transmission dynamics differ among these pathogens and are reflected in the pathogen-vector interaction. Anaplasma marginale has been shown to establish and maintain infectivity within Dermacentor spp. for weeks to months while escaping the complex network of vacuolar peptidases that are responsible for digestion of the tick blood meal...
August 1, 2016: Applied and Environmental Microbiology
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