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https://www.readbyqxmd.com/read/28546026/the-crustin-like-peptide-plays-opposite-role-in-shrimp-immune-response-to-vibrio-alginolyticus-and-white-spot-syndrome-virus-wssv-infection
#1
Baozhen Sun, Zhi Wang, Fei Zhu
Crustin is an antimicrobial peptide (AMP) that plays a key role in innate immunity of crustaceans. In this study, we cloned the entire 660 bp crustin-like sequence with a 507 bp open reading frame encoding a 168 amino acid from Marsupenaeus japonicus. The crustin-like gene was primarily expressed in gills and over-expressed in shrimp hemocytes after challenge with WSSV or Vibrio alginolyticus. After knockdown crustin-like gene using specific double-stranded RNA (CRU-dsRNA), IMD, Rab7, L-lectin, mitogen-activated protein kinase, p53, prophenoloxidase and Rho were down-regulated and nitric oxide synthase, myosin and tumor necrosis factor-α were up-regulated in hemocytes at 24 h post dsRNA treatment...
May 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28539733/molecular-docking-of-phytoligands-to-the-viral-protein-receptor-p-monodon-rab7
#2
Jerrine Joseph, Raj Bhaskaran, Muthusamy Kaliraj, Muthiyah Muthuswamy, Arumugam Suresh
The development of shrimp aquaculture has been severely affected by viral diseases resulting in a huge economic burden to the industry. White spot disease (WSD) has caused severe mortality in farmed shrimp in many countries. Globally aquaculture industries face huge economic losses due to rapid spread of White Spot Syndrome Virus (WSSV) disease that can cause 100% mortality in a short period of 3-10 days. In the present study in order to prevent the spread of WSSV disease in shrimps, the receptor, PmRab7 has been chosen as the drug target...
2017: Bioinformation
https://www.readbyqxmd.com/read/28526875/endophilinas-regulate-endosomal-sorting-of-bdnf-trkb-to-mediate-survival-signaling-in-hippocampal-neurons
#3
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/28483915/rab2-promotes-autophagic-and-endocytic-lysosomal-degradation
#4
Péter Lőrincz, Sarolta Tóth, Péter Benkő, Zsolt Lakatos, Attila Boda, Gábor Glatz, Martina Zobel, Sara Bisi, Krisztina Hegedűs, Szabolcs Takáts, Giorgio Scita, Gábor Juhász
Rab7 promotes fusion of autophagosomes and late endosomes with lysosomes in yeast and metazoan cells, acting together with its effector, the tethering complex HOPS. Here we show that another small GTPase, Rab2, is also required for autophagosome and endosome maturation and proper lysosome function in Drosophila melanogaster We demonstrate that Rab2 binds to HOPS, and that its active, GTP-locked form associates with autolysosomes. Importantly, expression of active Rab2 promotes autolysosomal fusions unlike that of GTP-locked Rab7, suggesting that its amount is normally rate limiting...
May 8, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28465352/cystinosin-the-small-gtpase-rab11-and-the-rab7-effector-rilp-regulate-intracellular-trafficking-of-the-chaperone-mediated-autophagy-receptor-lamp2a
#5
Jinzhong Zhang, Jennifer L Johnson, Jing He, Gennaro Napolitano, Mahalakshmi Ramadass, Celine Rocca, William B Kiosses, Cecilia Bucci, Qisheng Xin, Evripidis Gavathiotis, Ana María Cuervo, Stephanie Cherqui, Sergio D Catz
The lysosomal storage disease cystinosis, caused by cystinosin-deficiency, is characterized by cell malfunction, tissue failure and progressive renal injury despite cystine-depletion therapies. Cystinosis is associated with defects in chaperone-mediated autophagy (CMA), but the molecular mechanisms are incompletely understood. Here, we show CMA substrate accumulation in cystinotic kidney proximal tubule cells. We also found mislocalization of the CMA lysosomal receptor LAMP2A, and impaired substrate translocation into the lysosome caused by defective CMA in cystinosis...
May 2, 2017: Journal of Biological Chemistry
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
#6
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/28422978/the-escrt-regulator-did2-maintains-the-balance-between-long-distance-endosomal-transport-and-endocytic-trafficking
#7
Carl Haag, Thomas Pohlmann, Michael Feldbrügge
In highly polarised cells, like fungal hyphae, early endosomes function in both endocytosis as well as long-distance transport of various cargo including mRNA and protein complexes. However, knowledge on the crosstalk between these seemingly different trafficking processes is scarce. Here, we demonstrate that the ESCRT regulator Did2 coordinates endosomal transport in fungal hyphae of Ustilago maydis. Loss of Did2 results in defective vacuolar targeting, less processive long-distance transport and abnormal shuttling of early endosomes...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28415797/rab7-gtpase-controls-lipid-metabolic-signaling-in-myeloid-derived-suppressor-cells
#8
Xinchun Ding, Wenjing Zhang, Ting Zhao, Cong Yan, Hong Du
Lysosomal acid lipase (LAL) is a critical neutral lipid metabolic enzyme that regulates metabolic reprogramming in myeloid-derived suppressor cells (MDSCs) through over-activation of mammalian target of rapamycin (mTOR). Affymetrix GeneChip microarray analysis of MDSCs from LAL deficient mouse (lal-/-) revealed upregulation of Rab7 GTPase protein, which belongs to a superfamily of small-molecular-weight GTPase known to regulate intracellular membrane trafficking from early to late endosomes and lysosomes. Here, the physical protein-protein interaction between Rab7 GTPase and mTOR has been detected by co-immunoprecipitation in the cell extract of wild type HD1A and lal-/- MDSC-like HD1B myeloid cell lines...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415719/endosomal-sorting-and-c-cbl-targeting-of-paxillin-to-autophagosomes-regulate-cell-matrix-adhesion-turnover-in-human-breast-cancer-cells
#9
Chia-Hao Chang, Krikor Bijian, Dinghong Qiu, Jie Su, Amine Saad, Michael S Dahabieh, Wilson H Miller, Moulay A Alaoui-Jamali
Post-translational mechanisms regulating cell-matrix adhesion turnover during cell locomotion are not fully elucidated. In this study, we uncovered an essential role of Y118 site-specific tyrosine phosphorylation of paxillin, an adapter protein of focal adhesion complexes, in paxillin recruitment to autophagosomes to trigger turnover of peripheral focal adhesions in human breast cancer cells. We demonstrate that the Rab-7 GTPase is a key upstream regulator of late endosomal sorting of tyrosine118-phosphorylated paxillin, which is subsequently recruited to autophagosomes via the cargo receptor c-Cbl...
May 9, 2017: Oncotarget
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
#10
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/28394828/rab7-a-novel-redox-target-that-modulates-inflammatory-pain-processing
#11
Wiebke Kallenborn-Gerhardt, Christine V Möser, Jana E Lorenz, Mirco Steger, Juliana Heidler, Reynir Scheving, Jonas Petersen, Lea Kennel, Cathrin Flauaus, Ruirui Lu, Aimee L Edinger, Irmgard Tegeder, Gerd Geisslinger, Heinrich Heide, Ilka Wittig, Achim Schmidtko
Chronic pain is accompanied by production of reactive oxygen species (ROS) in various cells that are important for nociceptive processing. Recent data indicate that ROS can trigger specific redox-dependent signaling processes, but the molecular targets of ROS signaling in the nociceptive system remain largely elusive. Here, we performed a proteome screen for pain-dependent redox regulation using an OxICAT approach, thereby identifying the small GTPase Rab7 as a redox-modified target during inflammatory pain in mice...
April 7, 2017: Pain
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
#12
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/28347754/cadmium-disrupts-autophagic-flux-by-inhibiting-cytosolic-ca-2-dependent-autophagosome-lysosome-fusion-in-primary-rat-proximal-tubular-cells
#13
Fei Liu, Xin-Yu Wang, Xu-Ping Zhou, Zong-Ping Liu, Xiang-Bin Song, Zhen-Yong Wang, Lin Wang
Previous studies have shown that subcellular Ca(2+) redistribution is involved in Cd-induced autophagy inhibition in primary rat proximal tubular (rPT) cells, but the mechanism remains unclear. In this study, the status of autophagic flux was monitored by the GFP and RFP tandemly tagged LC3 method. Pharmacological inhibition of cytosolic Ca(2+) concentration ([Ca(2+)]c) with 2-APB or BAPTA-AM significantly alleviated Cd-elevated yellow puncta formation and restored Cd-inhibited red puncta formation, while thapsigargin (TG) had the opposite regulatory effect, demonstrating that Cd-induced [Ca(2+)]c elevation inhibited the autophagic flux in rPT cells...
March 25, 2017: Toxicology
https://www.readbyqxmd.com/read/28336235/tyrosine-phosphorylation-of-rab7-by-src-kinase
#14
Xiaosi Lin, Jiaming Zhang, Lingqiu Chen, Yongjun Chen, Xiaohui Xu, Wanjin Hong, Tuanlao Wang
The small molecular weight GTPase Rab7 is a key regulator for late endosomal/lysosomal membrane trafficking, it was known that Rab7 is phosphorylated, but the corresponding kinase and the functional regulation of Rab7 phosphorylation remain unclear. We provide evidence here that Rab7 is a substrate of Src kinase, and is tyrosine-phosphorylated by Src, withY183 residue of Rab7 being the optimal phosphorylation site for Src. Further investigations demonstrated that the tyrosine phosphorylation of Rab7 depends on the guanine nucleotide binding activity of Rab7 and the activity of Src kinase...
March 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28330474/hypercholesterolemia-downregulates-autophagy-in-the-rat-heart
#15
Zoltán Giricz, Gábor Koncsos, Tomáš Rajtík, Zoltán V Varga, Tamás Baranyai, Csaba Csonka, Adrián Szobi, Adriana Adameová, Roberta A Gottlieb, Péter Ferdinandy
BACKGROUND: We have previously shown that efficiency of ischemic conditioning is diminished in hypercholesterolemia and that autophagy is necessary for cardioprotection. However, it is unknown whether isolated hypercholesterolemia disturbs autophagy or the mammalian target of rapamycin (mTOR) pathways. Therefore, we investigated whether isolated hypercholesterolemia modulates cardiac autophagy-related pathways or programmed cell death mechanisms such as apoptosis and necroptosis in rat heart...
March 23, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28325809/the-rab7-effector-plekhm1-binds-arl8b-to-promote-cargo-traffic-to-lysosomes
#16
Rituraj Marwaha, Subhash B Arya, Divya Jagga, Harmeet Kaur, Amit Tuli, Mahak Sharma
Endocytic, autophagic, and phagocytic vesicles move on microtubule tracks to fuse with lysosomes. Small GTPases, such as Rab7 and Arl8b, recruit their downstream effectors to mediate this transport and fusion. However, the potential cross talk between these two GTPases is unclear. Here, we show that the Rab7 effector PLEKHM1 simultaneously binds Rab7 and Arl8b, bringing about clustering and fusion of late endosomes and lysosomes. We show that the N-terminal RUN domain of PLEKHM1 is necessary and sufficient for interaction with Arl8b and its subsequent localization to lysosomes...
April 3, 2017: Journal of Cell Biology
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
#17
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/28291748/the-crystal-structure-of-mouse-lc3b-in-complex-with-the-fyco1-lir-reveals-the-importance-of-the-flanking-region-of-the-lir-motif
#18
Shunya Sakurai, Taisuke Tomita, Toshiyuki Shimizu, Umeharu Ohto
FYVE and coiled-coil domain-containing protein 1 (FYCO1), a multidomain autophagy adaptor protein, mediates microtubule plus-end-directed autophagosome transport by interacting with kinesin motor proteins and with the autophagosomal membrane components microtubule-associated protein 1 light chain 3 (LC3), Rab7 and phosphatidylinositol 3-phosphate (PI3P). To establish the structural basis for the recognition of FYCO1 by LC3, the crystal structure of mouse LC3B in complex with the FYCO1 LC3-interacting region (LIR) motif peptide was determined...
March 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28275133/ppar-%C3%AE-activation-mediates-innate-host-defense-through-induction-of-tfeb-and-lipid-catabolism
#19
Yi Sak Kim, Hye-Mi Lee, Jin Kyung Kim, Chul-Su Yang, Tae Sung Kim, Mingyu Jung, Hyo Sun Jin, Sup Kim, Jichan Jang, Goo Taeg Oh, Jin-Man Kim, Eun-Kyeong Jo
The role of peroxisome proliferator-activated receptor α (PPAR-α) in innate host defense is largely unknown. In this study, we show that PPAR-α is essential for antimycobacterial responses via activation of transcription factor EB (TFEB) transcription and inhibition of lipid body formation. PPAR-α deficiency resulted in an increased bacterial load and exaggerated inflammatory responses during mycobacterial infection. PPAR-α agonists promoted autophagy, lysosomal biogenesis, phagosomal maturation, and antimicrobial defense against Mycobacterium tuberculosis or M...
March 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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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