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Rab5

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https://www.readbyqxmd.com/read/28529514/two-rab5-homologs-are-essential-for-the-development-and-pathogenicity-of-the-rice-blast-fungus-magnaporthe-oryzae
#1
Cheng D Yang, Xie Dang, Hua W Zheng, Xiao F Chen, Xiao L Lin, Dong M Zhang, Yakubu S Abubakar, Xin Chen, Guodong Lu, Zonghua Wang, Guangpu Li, Jie Zhou
The rice blast fungus, Magnaporthe oryzae, infects many economically important cereal crops, particularly rice. It has emerged as an important model organism for studying the growth, development, and pathogenesis of filamentous fungi. RabGTPases are important molecular switches in regulation of intracellular membrane trafficking in all eukaryotes. MoRab5A and MoRab5B are Rab5 homologs in M. oryzae, but their functions in the fungal development and pathogenicity are unknown. In this study, we have employed a genetic approach and demonstrated that both MoRab5A and MoRab5B are crucial for vegetative growth and development, conidiogenesis, melanin synthesis, vacuole fusion, endocytosis, sexual reproduction, and plant pathogenesis in M...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28526875/endophilinas-regulate-endosomal-sorting-of-bdnf-trkb-to-mediate-survival-signaling-in-hippocampal-neurons
#2
Katja Burk, John D Murdoch, Siona Freytag, Melanie Koenig, Vinita Bharat, Ronja Markworth, Susanne Burkhardt, Andre Fischer, Camin Dean
The sorting of activated receptors into distinct endosomal compartments is essential to activate specific signaling cascades and cellular events including growth and survival. However, the proteins involved in this sorting are not well understood. We discovered a novel role of EndophilinAs in sorting of activated BDNF-TrkB receptors into late endosomal compartments. Mice lacking all three EndophilinAs accumulate Rab7-positive late endosomes. Moreover, EndophilinAs are differentially localized to, co-traffic with, and tubulate, distinct endosomal compartments: In response to BDNF, EndophilinA2 is recruited to both early and late endosomes, EndophilinA3 is recruited to Lamp1-positive late endosomes, and co-trafficks with Rab5 and Rab7 in both the presence and absence of BDNF, while EndophilinA1 colocalizes at lower levels with endosomes...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28507272/phosphatidylinositol-5-phosphate-4-kinase-regulates-early-endosomal-dynamics-during-clathrin-mediated-endocytosis
#3
Kumari Kamalesh, Deepti Trivedi, Sarah Toscano, Sanjeev Sharma, Sourav Kolay, Padinjat Raghu
Endocytic turnover is essential to regulate the protein composition and function of the plasma membrane thus regulating the plasma membrane levels of many receptors. In Drosophila photoreceptors, photon absorption by the GPCR rhodopsin 1 (Rh1) triggers its endocytosis by clathrin-mediated endocytosis (CME). We find that CME of Rh1 is regulated by phosphatidylinositol 5 phosphate 4-kinase (PIP4K). Flies lacking PIP4K show mislocalization of Rh1 on expanded endomembranes within the cell body. This mislocalization of Rh1 was dependent on the formation of an expanded Rab5 compartment...
May 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28491025/change-of-rin1-and-stathmin-in-the-animal-model-of-traumatic-stresses
#4
Fang Han, Jingzhi Jiang, Jinlan Ding, Hong Liu, Bing Xiao, Yuxiu Shi
The molecular mechanism of fear memory is poorly understood. Therefore, the pathogenesis of post-traumatic stress disorder (PTSD), whose symptom presentation can enhance fear memory, remains largely unclear. Recent studies with knockout animals have reported that Rin1 and stathmin regulate fear memory. Rin1 inhibits acquisition and promotes memory extinction, whereas stathmin regulates innate and basal fear. The aim of our study was to examine changes in the expression of Rin1 and stathmin in different animal models of stress, particluarly traumatic stress...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28489965/evidence-for-the-subsynaptic-zone-as-a-preferential-site-for-chrn-recycling-at-neuromuscular-junctions
#5
Franziska Wild, Muzamil Majid Khan, Rüdiger Rudolf
Vertebrate skeletal muscle contraction is mediated by nicotinic acetylcholine receptors (CHRN). Endocytosis and recycling of CHRN regulate their proper abundance at nerve-muscle synapses, i.e. neuromuscular junctions. Recent work showed that RAB5 is essential for CHRN endocytosis. Here, using in vivo-imaging of endocytosed CHRN and RAB-GFP fusion proteins, we deliver evidence for differential effects of RAB5-GFP, RAB4-GFP, and RAB11-GFP on CHRN endocytosis. Furthermore, while newly endocytosed CHRN colocalized with RAB5-GFP over large stretches of muscle fibers, RAB4-GFP and RAB11-GFP colocalized with endocytosed CHRN almost exclusively at neuromuscular junctions...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28482024/vps35-in-cooperation-with-lrrk2-regulates-synaptic-vesicle-endocytosis-through-the-endosomal-pathway-in-drosophila
#6
Tsuyoshi Inoshita, Taku Arano, Yuka Hosaka, Hongrui Meng, Yujiro Umezaki, Sakiko Kosugi, Takako Morimoto, Masato Koike, Hui-Yun Chang, Yuzuru Imai, Nobutaka Hattori
Mutations of the retromer component Vps35 and endosomal kinase LRRK2 are linked to autosomal dominant forms of familial Parkinson's disease (PD). However, the physiological and pathological roles of Vps35 and LRRK2 in neuronal functions are poorly understood. Here, we demonstrated that the loss of Drosophila Vps35 (dVps35) affects synaptic vesicle recycling, dopaminergic synaptic release and sleep behavior associated with dopaminergic activity, which is rescued by the expression of wild-type dVps35 but not the PD-associated mutant dVps35 D647N...
May 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28455411/the-vps-34-pi3-kinase-negatively-regulates-rab-5-during-endosome-maturation
#7
Fiona Law, Jung Hwa Seo, Ziqing Wang, Jennifer L DeLeon, Yousstina Bolis, Ashley Brown, Wei-Xing Zong, Guangwei Du, Christian E Rocheleau
The Rab5 GTPase and phosphatidylinositol-3 phosphate (PI(3)P) coordinately regulate endosome trafficking. Rab5 recruits Vps34, the class III PI3-kinase (PI3K), to generate PI(3)P and recruit PI(3)P binding proteins. Loss of Rab5 and loss of Vps34 have opposite effects on endosome size suggesting that our understanding of how Rab5 and PI(3)P cooperate is incomplete. Here we report a novel regulatory loop, whereby C. elegans VPS-34 inactivates RAB-5 via recruitment of the TBC-2 Rab GTPase Activating Protein. We found that loss of VPS-34 caused a large late endosome phenotype like that of loss of TBC-2, and that Rab5 activity is increased in Vps34 knockout mouse embryonic fibroblasts...
April 28, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28455099/membrane-localization-and-dynamics-of-geranylgeranylated-rab5-hypervariable-region
#8
Eileen Edler, Eric Schulze, Matthias Stein
The small GTPase Rab5 is a key regulator of endosomal trafficking processes and a marker for the early endosome. The C-terminal hypervariable region (HVR) of Rab5 is post-translationally modified at residues Cys(212) and Cys(213) to accommodate two geranylgeranyl anchors (C20 carbon chain length) in order to associate Rab5 with the membrane. The structural role of the HVR regarding protein-early endosome membrane recruitment is not resolved due to its high degree of flexibility and lack of crystallographic information...
April 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28442548/keratin-8-18-regulation-of-insulin-receptor-signaling-and-trafficking-in-hepatocytes-through-a-concerted-phosphoinositide-dependent-akt-and-rab5-modulation
#9
Alexandra Roux, Anne Loranger, Josée N Lavoie, Normand Marceau
Keratins (Ks) are epithelial cell intermediate filament (IF) proteins that are expressed as pairs in a differentiation-regulated manner. Hepatocyte IFs are made only of K8/K18 pairs, which means that a K8 loss in K8-null mice leads to degradation of K18. Functionally, there is accumulating evidence that IFs contribute to signaling platforms. Here, we investigate the role of K8/K18 IFs in the regulation of insulin receptor (IR) signaling and trafficking in hepatocytes. We find that the IR substrate 1 (IRS1)/PI3K/Akt signaling cascade-downstream of IR-display prolonged activation in K8-null compared with wild-type hepatocytes...
April 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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
#10
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/28420712/sec71-functions-as-a-gef-for-the-small-gtpase-arf1-to-govern-dendrite-pruning-of-drosophila-sensory-neurons
#11
Yan Wang, Heng Zhang, Meng Shi, Yih-Cherng Liou, Lei Lu, Fengwei Yu
Pruning, whereby neurons eliminate their exuberant neurites, is central for the maturation of the nervous system. In Drosophila, sensory neurons, ddaCs, selectively prune their larval dendrites without affecting their axons during metamorphosis. However, it is unknown whether the secretory pathway plays a role in dendrite pruning. Here, we show that the small GTPase Arf1, an important regulator of secretory pathway, is specifically required for dendrite pruning of ddaC/D/E sensory neurons but dispensable for apoptosis of ddaF neurons...
April 18, 2017: Development
https://www.readbyqxmd.com/read/28408870/homeostatic-changes-in-gaba-and-glutamate-receptors-on-excitatory-cortical-neurons-during-sleep-deprivation-and-recovery
#12
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/28396666/dynamic-changes-in-the-intracellular-association-of-selected-rab-small-gtpases-with-mhc-class-ii-and-dm-during-dendritic-cell-maturation
#13
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/28348980/overexpression-of-the-endosomal-anion-proton-exchanger-clc-5-increases-cell-susceptibility-toward-clostridium-difficile-toxins-tcda-and-tcdb
#14
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/28341445/insulin-promotes-cell-migration-by-regulating-psa-ncam
#15
Hector J Monzo, Natacha Coppieters, Thomas I H Park, Birger V Dieriks, Richard L M Faull, Mike Dragunow, Maurice A Curtis
Cellular interactions with the extracellular environment are modulated by cell surface polysialic acid (PSA) carried by the neural cell adhesion molecule (NCAM). PSA-NCAM is involved in cellular processes such as differentiation, plasticity, and migration, and is elevated in Alzheimer's disease as well as in metastatic tumour cells. Our previous work demonstrated that insulin enhances the abundance of cell surface PSA by inhibiting PSA-NCAM endocytosis. In the present study we have identified a mechanism for insulin-dependent inhibition of PSA-NCAM turnover affecting cell migration...
March 21, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28317806/mycobacterium-lepraemurium-uses-tlr-6-and-mr-but-not-lipid-rafts-or-dc-sign-to-gain-access-into-mouse-macrophages
#16
Mayra Silva-Miranda, Patricia Arce-Paredes, Oscar Rojas-Espinosa
OBJECTIVE/BACKGROUND: Mycobacterium lepraemurium (MLM), the etiologic agent of murine leprosy, is an intracellular parasite of macrophages; the mechanism used by this bacterium to enter macrophages is not known. The fate of the MLM phagosome inside macrophages is also unknown. This study was conducted to investigate how MLM enters macrophages and to define the maturation process of MLM phagosome inside macrophages. MATERIALS AND METHODS: Peritoneal macrophages were incubated in the presence of mannan-bovine serum albumin (BSA), and antibodies to known macrophage receptors, including, anti-FcγRIII/RII (anti-CD16/32), anti-CD35 (anti-CR1), anti-TLR2, anti-TLR4, anti-TLR6, anti-CD14, and anti-dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)...
January 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28315838/germline-proliferation-is-regulated-by-somatic-endocytic-genes-via-jnk-and-bmp-signaling-in-drosophila
#17
Yaning Tang, Qing Geng, Di Chen, Shaowei Zhao, Xian Liu, Zhaohui Wang
Signals derived from the microenvironment contribute greatly to tumorigenesis . The underlying mechanism requires thorough investigation. Here, we use Drosophila testis as a model system to address this question, taking the advantage of the ease to distinguish germline and somatic cells and to track the cell numbers. In an EMS mutagenesis screen, we identified Rab5, a key factor in endocytosis, for its nonautonomous role in germline proliferation. The disruption of Rab5 in somatic cyst cells, which escort the development of germline lineage, induced the overproliferation of underdifferentiated but genetically wild-type germ cells...
May 2017: Genetics
https://www.readbyqxmd.com/read/28302665/calpain-mobilizes-atg9-bif-1-vesicles-from-golgi-stacks-upon-autophagy-induction-by-thapsigargin
#18
Elena Marcassa, Marzia Raimondi, Tahira Anwar, Eeva-Liisa Eskelinen, Michael P Myers, Gianluca Triolo, Claudio Schneider, Francesca Demarchi
CAPNS1 is essential for stability and function of the ubiquitous calcium-dependent proteases micro- and milli-calpain. Upon inhibition of the endoplasmic reticulum Ca(2+) ATPase by 100 nM thapsigargin, both micro-calpain and autophagy are activated in human U2OS osteosarcoma cells in a CAPNS1-dependent manner. As reported for other autophagy triggers, thapsigargin treatment induces Golgi fragmentation and fusion of Atg9/Bif-1-containing vesicles with LC3 bodies in control cells. By contrast, CAPNS1 depletion is coupled with an accumulation of LC3 bodies and Rab5 early endosomes...
May 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28270608/rab5-regulated-endocytosis-plays-a-crucial-role-in-apical-extrusion-of-transformed-cells
#19
Sayaka Saitoh, Takeshi Maruyama, Yuta Yako, Mihoko Kajita, Yoichiro Fujioka, Yusuke Ohba, Nobuhiro Kasai, Natsu Sugama, Shunsuke Kon, Susumu Ishikawa, Takashi Hayashi, Tomohiro Yamazaki, Masazumi Tada, Yasuyuki Fujita
Newly emerging transformed cells are often eliminated from epithelial tissues. Recent studies have revealed that this cancer-preventive process involves the interaction with the surrounding normal epithelial cells; however, the molecular mechanisms underlying this phenomenon remain largely unknown. In this study, using mammalian cell culture and zebrafish embryo systems, we have elucidated the functional involvement of endocytosis in the elimination of RasV12-transformed cells. First, we show that Rab5, a crucial regulator of endocytosis, is accumulated in RasV12-transformed cells that are surrounded by normal epithelial cells, which is accompanied by up-regulation of clathrin-dependent endocytosis...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28264927/missing-in-metastasis-protein-downregulates-cxcr4-by-promoting-ubiquitylation-and-interaction-with-small-rab-gtpases
#20
Lushen Li, Shaneen S Baxter, Ning Gu, Min Ji, Xi Zhan
Surface expression of chemokine receptor CXCR4 is downregulated by missing-in-metastasis protein (MIM; also known as MTSS1), a member of the inverse BAR (I-BAR)-domain protein family that recognizes and generates membranes with negative curvature. Yet, the mechanism for the regulation is unknown. Here, we show that MIM forms a complex with CXCR4 by binding to E3 ubiquitin ligase AIP4 (also known as ITCH) in response to stromal cell-derived factor 1 (SDF-1; also known as CXCL12). Overexpression of MIM promoted CXCR4 ubiquitylation, inhibited cellular response to SDF-1, caused accumulation and aggregation of multivesicular bodies (MVBs) in the cytoplasm, and promoted CXCR4 sorting into MVBs in a manner depending on binding to AIP4...
April 15, 2017: Journal of Cell Science
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