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https://www.readbyqxmd.com/read/28225130/systematic-investigation-on-the-intracellular-trafficking-network-of-polymeric-nanoparticles
#1
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/28185347/salmonella-effector-sopd2-interferes-with-rab34-function
#2
Wei Xuan Teo, Zhe Yang, Markus Charles Kerr, Lin Luo, Zhong Guo, Kirill Alexandrov, Jenny Lea Stow, Rohan David Teasdale
Many intracellular pathogens have evolved highly specialized mechanisms to isolate themselves from the host cell's innate immune response while still obtaining the necessary nutrients to survive. Salmonella utilizes type 3 secretion systems (T3SSs) to deliver bacterial proteins called effectors, across the encompassing Salmonella Containing vacuole (SCV) membrane, to subvert the host's membrane trafficking pathways and alter other cellular processes. The Salmonella Pathogenicity Island (SPI)-2 effector SopD2 has recently been demonstrated to modulate multiple members of the Rab GTPase family such as Rab7, Rab8, Rab10, and Rab32 (D'Costa et al...
February 9, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28132130/rab10-disruption-results-in-delayed-opc-maturation
#3
Zhao-Huan Zhang, Wei-Qian Zhao, Fan-Fei Ma, Hui Zhang, Xiao-Hui Xu
Oligodendrocyte precursor cell (OPC) maturation requires membrane addition for myelin sheath formation. Since the Rab system has been shown to contribute to membrane addition in other cell types, in this study, we explored the role of Rab in OPC maturation. SiRNA and shRNA techniques and conditional knockout mice provided in vitro and in vivo evidence that Rab10 is involved in OPC maturation and may affect myelination during OPC development.
January 28, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28079153/nf-%C3%AE%C2%BAb-activation-is-critical-for-bacterial-lipoprotein-tolerance-enhanced-bactericidal-activity-in-macrophages-during-microbial-infection
#4
Jinghua Liu, Jing Xiang, Xue Li, Siobhan Blankson, Shuqi Zhao, Junwei Cai, Yong Jiang, H Paul Redmond, Jiang Huai Wang
Tolerance to bacterial components represents an essential regulatory mechanism during bacterial infection. Bacterial lipoprotein (BLP)-induced tolerance confers protection against microbial sepsis by attenuating inflammatory responses and augmenting antimicrobial activity in innate phagocytes. It has been well-documented that BLP tolerance-attenuated proinflammatory cytokine production is associated with suppressed TLR2 signalling pathway; however, the underlying mechanism(s) involved in BLP tolerance-enhanced antimicrobial activity is unclear...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067790/rab10-interacts-with-the-male-germ-cell-specific-gtpase-activating-protein-during-mammalian-spermiogenesis
#5
Ying-Hung Lin, Chih-Chun Ke, Ya-Yun Wang, Mei-Feng Chen, Tsung-Ming Chen, Wei-Chi Ku, Han-Sun Chiang, Chung-Hsin Yeh
According to recent estimates, 2%-15% of couples are sterile, and approximately half of the infertility cases are attributed to male reproductive factors. However, the reasons remain undefined in approximately 25% of male infertility cases, and most infertility cases exhibit spermatogenic defects. Numerous genes involved in spermatogenesis still remain unknown. We previously identified Male Germ Cells Rab GTPase-Activating Proteins (MGCRABGAPs) through cDNA microarray analysis of human testicular tissues with spermatogenic defects...
January 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28028537/a-novel-rab10-ehbp1-ehd2-complex-essential-for-the-autophagic-engulfment-of-lipid-droplets
#6
Zhipeng Li, Ryan J Schulze, Shaun G Weller, Eugene W Krueger, Micah B Schott, Xiaodong Zhang, Carol A Casey, Jun Liu, Jacqueline Stöckli, David E James, Mark A McNiven
The autophagic digestion of lipid droplets (LDs) through lipophagy is an essential process by which most cells catabolize lipids as an energy source. However, the cellular machinery used for the envelopment of LDs during autophagy is poorly understood. We report a novel function for a small Rab guanosine triphosphatase (GTPase) in the recruitment of adaptors required for the engulfment of LDs by the growing autophagosome. In hepatocytes stimulated to undergo autophagy, Rab10 activity is amplified significantly, concomitant with its increased recruitment to nascent autophagic membranes at the LD surface...
December 2016: Science Advances
https://www.readbyqxmd.com/read/28009298/adenovirus-protein-e4-orf1-activation-of-pi3-kinase-reveals-differential-regulation-of-downstream-effector-pathways-in-adipocytes
#7
Natasha Chaudhary, Eva Gonzalez, Sung-Hee Chang, Fuqiang Geng, Shahin Rafii, Nasser K Altorki, Timothy E McGraw
Insulin activation of phosphatidylinositol 3-kinase (PI3K) regulates metabolism, including the translocation of the Glut4 glucose transporter to the plasma membrane and inactivation of the FoxO1 transcription factor. Adenoviral protein E4-ORF1 stimulates cellular glucose metabolism by mimicking growth-factor activation of PI3K. We have used E4-ORF1 as a tool to dissect PI3K-mediated signaling in adipocytes. E4-ORF1 activation of PI3K in adipocytes recapitulates insulin regulation of FoxO1 but not regulation of Glut4...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/27698943/intracellular-trafficking-network-of-protein-nanocapsules-endocytosis-exocytosis-and-autophagy
#8
Jinxie Zhang, Xudong Zhang, Gan Liu, Danfeng Chang, Xin Liang, Xianbing Zhu, Wei Tao, Lin Mei
The inner membrane vesicle system is a complex transport system that includes endocytosis, exocytosis and autophagy. However, the details of the intracellular trafficking pathway of nanoparticles in cells have been poorly investigated. Here, we investigate in detail the intracellular trafficking pathway of protein nanocapsules using more than 30 Rab proteins as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy. We observed that FITC-labeled protein nanoparticles were internalized by the cells mainly through Arf6-dependent endocytosis and Rab34-mediated micropinocytosis...
2016: Theranostics
https://www.readbyqxmd.com/read/27687479/rab3a-and-rab10-are-regulators-of-lysosome-exocytosis-and-plasma-membrane-repair
#9
Otilia V Vieira
Disruption of the cell plasma membrane can occur due to mechanical damage, pore forming toxins, etc. Resealing or plasma membrane repair (PMR) is the emergency response required for cell survival. It is triggered by Ca(2+) entering through the disruption, causing organelles such as lysosomes located underneath the plasma membrane to fuse rapidly with the adjacent plasma membrane. We have recently identified some of the molecular traffic machinery that is involved in this vital process. Specifically, we showed that 2 members of the Rab family of small GTPases, Rab3a and Rab10, are essential for lysosome exocytosis and PMR in cells challenged with a bacterial toxin, streptolysin-O (SLO)...
September 29, 2016: Small GTPases
https://www.readbyqxmd.com/read/27621483/-up-with-the-lrrk-a-phosphorylated-rab10-assay-for-evaluation-of-lrrk2-activity-and-inhibitor-engagement
#10
Patrick A Eyers
Protein kinases catalyse the addition of phosphate groups to Ser/Thr and Tyr residues in cognate substrates and are mutated or hyperactive in a variety of diseases, making them important targets for rationally designed drugs. A good example is the Parkinson's disease-associated kinase, leucine-rich repeat kinase 2 (LRRK2), which is mutated (and probably hyperactive) in a small, but significant, subset of patients. An exciting new approach for personalised therapy is the development of central nervous system (CNS)-active small-molecule kinase inhibitors, which could be employed to 'normalise' LRRK2 signalling in affected cell types...
September 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27474410/phos-tag-analysis-of-rab10-phosphorylation-by-lrrk2-a-powerful-assay-for-assessing-kinase-function-and-inhibitors
#11
Genta Ito, Kristina Katsemonova, Francesca Tonelli, Pawel Lis, Marco A S Baptista, Natalia Shpiro, Graham Duddy, Steve Wilson, Philip Wing-Lok Ho, Shu-Leong Ho, Alastair D Reith, Dario R Alessi
Autosomal dominant mutations that activate the leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson's disease. Recent work has revealed that LRRK2 directly phosphorylates a conserved threonine/serine residue in the effector-binding switch-II motif of a number of Rab GTPase proteins, including Rab10. Here we describe a facile and robust method to assess phosphorylation of endogenous Rab10 in mouse embryonic fibroblasts (MEFs), lung and spleen-derived B-cells, based on the ability of the Phos-tag reagent to retard the electrophoretic mobility of LRRK2-phosphorylated Rab10...
September 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27404358/rab10-mediated-secretion-synergizes-with-tissue-movement-to-build-a-polarized-basement-membrane-architecture-for-organ-morphogenesis
#12
Adam J Isabella, Sally Horne-Badovinac
Basement membranes (BMs) are planar protein networks that support epithelial function. Regulated changes to BM architecture can also contribute to tissue morphogenesis, but how epithelia dynamically remodel their BMs is unknown. In Drosophila, elongation of the initially spherical egg chamber correlates with the generation of a polarized network of fibrils in its surrounding BM. Here, we use live imaging and genetic manipulations to determine how these fibrils form. BM fibrils are assembled from newly synthesized proteins in the pericellular spaces between the egg chamber's epithelial cells and undergo oriented insertion into the BM by directed epithelial migration...
July 11, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27404350/tissue-sculpting-by-fibrils
#13
Ranjay Jayadev, David R Sherwood
In this issue of Developmental Cell, Isabella and Horne-Badovinac (2016) show that Rab10 directs site-specific secretion of basement membrane components, which assemble into fibrils that spool out to elongate the Drosophila egg chamber. These findings establish the basement membrane's active role in tissue sculpting.
July 11, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27354378/sec16a-is-a-rab10-effector-required-for-insulin-stimulated-glut4-trafficking-in-adipocytes
#14
Joanne Bruno, Alexandria Brumfield, Natasha Chaudhary, David Iaea, Timothy E McGraw
RAB10 is a regulator of insulin-stimulated translocation of the GLUT4 glucose transporter to the plasma membrane (PM) of adipocytes, which is essential for whole-body glucose homeostasis. We establish SEC16A as a novel RAB10 effector in this process. Colocalization of SEC16A with RAB10 is augmented by insulin stimulation, and SEC16A knockdown attenuates insulin-induced GLUT4 translocation, phenocopying RAB10 knockdown. We show that SEC16A and RAB10 promote insulin-stimulated mobilization of GLUT4 from a perinuclear recycling endosome/TGN compartment...
July 4, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27272733/rab-10-promotes-ehbp-1-bridging-of-filamentous-actin-and-tubular-recycling-endosomes
#15
Peixiang Wang, Hang Liu, Yu Wang, Ou Liu, Jing Zhang, Adenrele Gleason, Zhenrong Yang, Hui Wang, Anbing Shi, Barth D Grant
EHBP-1 (Ehbp1) is a conserved regulator of endocytic recycling, acting as an effector of small GTPases including RAB-10 (Rab10). Here we present evidence that EHBP-1 associates with tubular endosomal phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] enriched membranes through an N-terminal C2-like (NT-C2) domain, and define residues within the NT-C2 domain that mediate membrane interaction. Furthermore, our results indicate that the EHBP-1 central calponin homology (CH) domain binds to actin microfilaments in a reaction that is stimulated by RAB-10(GTP)...
June 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27207531/disruption-of-adipose-rab10-dependent-insulin-signaling-causes-hepatic-insulin-resistance
#16
Reema P Vazirani, Akanksha Verma, L Amanda Sadacca, Melanie S Buckman, Belen Picatoste, Muheeb Beg, Christopher Torsitano, Joanne H Bruno, Rajesh T Patel, Kotryna Simonyte, Joao P Camporez, Gabriela Moreira, Domenick J Falcone, Domenico Accili, Olivier Elemento, Gerald I Shulman, Barbara B Kahn, Timothy E McGraw
Insulin controls glucose uptake into adipose and muscle cells by regulating the amount of GLUT4 in the plasma membrane. The effect of insulin is to promote the translocation of intracellular GLUT4 to the plasma membrane. The small Rab GTPase, Rab10, is required for insulin-stimulated GLUT4 translocation in cultured 3T3-L1 adipocytes. Here we demonstrate that both insulin-stimulated glucose uptake and GLUT4 translocation to the plasma membrane are reduced by about half in adipocytes from adipose-specific Rab10 knockout (KO) mice...
June 2016: Diabetes
https://www.readbyqxmd.com/read/27170183/rabin8-regulates-neurite-outgrowth-in-both-gef-activity-dependent-and-independent-manners
#17
Yuta Homma, Mitsunori Fukuda
Many aspects of membrane-trafficking events are regulated by Rab-family small GTPases. Neurite outgrowth requires massive addition of proteins and lipids to the tips of growing neurites by membrane trafficking, and although several Rabs, including Rab8, Rab10, and Rab11, have been implicated in this process, their regulatory mechanisms during neurite outgrowth are poorly understood. Here, we show that Rabin8, a Rab8-guanine nucleotide exchange factor (GEF), regulates nerve growth factor (NGF)-induced neurite outgrowth of PC12 cells...
July 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/26973816/the-pathogen-occupied-vacuoles-of-anaplasma-phagocytophilum-and-anaplasma-marginale-interact-with-the-endoplasmic-reticulum
#18
Hilary K Truchan, Chelsea L Cockburn, Kathryn S Hebert, Forgivemore Magunda, Susan M Noh, Jason A Carlyon
The genus Anaplasma consists of tick-transmitted obligate intracellular bacteria that invade white or red blood cells to cause debilitating and potentially fatal infections. A. phagocytophilum, a human and veterinary pathogen, infects neutrophils to cause granulocytic anaplasmosis. A. marginale invades bovine erythrocytes. Evidence suggests that both species may also infect endothelial cells in vivo. In mammalian and arthropod host cells, A. phagocytophilum and A. marginale reside in host cell derived pathogen-occupied vacuoles (POVs)...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/26936971/rab14-limits-the-sorting-of-glut4-from-endosomes-into-insulin-sensitive-regulated-secretory-compartments-in-adipocytes
#19
Paul Duffield Brewer, Estifanos N Habtemichael, Irina Romenskaia, Adelle C F Coster, Cynthia Corley Mastick
Insulin increases glucose uptake by increasing the rate of exocytosis of the facilitative glucose transporter isoform 4 (Glut4) relative to its endocytosis. Insulin also releases Glut4 from highly insulin-regulated secretory compartments (GSVs or Glut4 storage vesicles) into constitutively cycling endosomes. Previously it was shown that both overexpression and knockdown of the small GTP-binding protein Rab14 decreased Glut4 translocation to the plasma membrane (PM). To determine the mechanism of this perturbation, we measured the effects of Rab14 knockdown on the trafficking kinetics of Glut4 relative to two proteins that partially co-localize with Glut4, the transferrin (Tf) receptor and low-density-lipoprotein-receptor-related protein 1 (LRP1)...
May 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/26775587/small-gtpases-in-peroxisome-dynamics
#20
REVIEW
Wilhelm W Just, Johan Peränen
In this review article, we summarize current knowledge on peroxisome biogenesis/functions and the role that small GTPases may play in these processes. Precise intracellular distribution of cell organelles requires their regulated association to microtubules and the actin cytoskeleton. In this respect, RhoGDP/RhoGTP favor binding of peroxisomes to microtubules and actin filaments. In its GTP-bound form, RhoA activates a regulatory cascade involving Rho kinaseII and non-muscle myosinIIA. Such interactions frequently depend on phosphoinositides (PIs) of which PI4P, PI(4,5)P2, and PI(3,5)P2 were found to be present in the peroxisomal membrane...
May 2016: Biochimica et Biophysica Acta
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