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https://www.readbyqxmd.com/read/28318878/insulin-stimulates-transport-of-organic-anion-compounds-mediated-by-organic-anion-transporting-polypeptide-2b1-in-the-human-intestinal-cell-line-caco-2
#1
Taku Kobayashi, Takahiro Koizumi, Masaki Kobayashi, Jiro Ogura, Yuichi Horiuchi, Yuki Kimura, Ayuko Kondo, Ayako Furugen, Katsuya Narumi, Natsuko Takahashi, Ken Iseki
Organic anion transporting polypeptide 2B1 (OATP2B1) is the major uptake transporter in the intestine, and transports various clinically used therapeutic agents. Insulin acts through the insulin receptor in targeted cells, and Rab8A is one of the insulin signaling pathways. The small intestine in humans also expresses insulin receptor and Rab8A. It has been reported that insulin stimulates peptide transporter 1 (PEPT1) expression at the apical membrane and increases uptake of PEPT1 substrates in small intestine epithelial model cells (Caco-2 cells)...
December 27, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28264818/trafficking-ion-transporters-to-the-apical-membrane-of-polarized-intestinal-enterocytes
#2
Amy Christine Engevik, James R Goldenring
Epithelial cells lining the gastrointestinal tract require distinct apical and basolateral domains to function properly. Trafficking and insertion of enzymes and transporters into the apical brush border of intestinal epithelial cells is essential for effective digestion and absorption of nutrients. Specific critical ion transporters are delivered to the apical brush border to facilitate fluid and electrolyte uptake. Maintenance of these apical transporters requires both targeted delivery and regulated membrane recycling...
March 6, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28130450/rab8a-recruited-pi3k%C3%AE-regulates-signaling-and-cytokine-outputs-from-endosomal-toll-like-receptors
#3
Adam A Wall, Lin Luo, Yu Hung, Samuel J Tong, Nicholas D Condon, Antje Blumenthal, Matthew J Sweet, Jennifer L Stow
Lipopolysaccharide (LPS)-mediated activation of Toll-like receptor 4 (TLR4) in macrophages results in the coordinated release of proinflammatory cytokines, followed by regulatory mediators, to ensure that this potentially destructive pathway is tightly regulated. We previously showed that Rab8a recruits PI3Kγ for Akt-dependent signaling during TLR4 activation to limit the production of the pro-inflammatory cytokines IL-6 and IL-12p40, while enhancing the release of the regulatory/anti-inflammatory cytokine IL-10...
January 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28123016/cdk5-regulation-of-the-grab-mediated-rab8-rab11-cascade-in-axon-outgrowth
#4
Kotaro Furusawa, Akiko Asada, Pamela Urrutia, Christian Gonzalez-Billault, Mitsunori Fukuda, Shin-Ichi Hisanaga
Neurons communicate with each other through their axons and dendrites. However, a full characterization of the molecular mechanisms involved in axon and dendrite formation is still incomplete. Neurite outgrowth requires the supply of membrane components for surface expansion. Two membrane sources for axon outgrowth are suggested: Golgi secretary vesicles and endocytic recycling endosomes. In non-neuronal cells, trafficking of secretary vesicles from Golgi is regulated by Rab8, a member of Rab small GTPases, and that of recycling endosomes is by Rab11, another member of Rabs...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28115417/the-parkinson-s-disease-linked-protein-tmem230-is-required-for-rab8a-mediated-secretory-vesicle-trafficking-and-retromer-trafficking
#5
Myung Jong Kim, Han-Xiang Deng, Yvette C Wong, Teepu Siddique, Dimitri Krainc
TMEM230 is a newly identified Parkinson's disease (PD) gene encoding a transmembrane protein whose cellular and pathogenic roles remain largely unknown. Here, we demonstrate that loss of TMEM230 disrupts retromer cargo CI-M6PR (cation-independent mannose 6-phosphate receptor) trafficking and autophagic cargo degradation rates. TMEM230 depletion further inhibits extracellular secretion of the autophagic cargo p62 and immature lysosomal hydrolases in Golgi-derived vesicles leading to their intracellular accumulation, and is specifically mediated by loss of the small GTPase Rab8a...
January 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28005071/rab8a-rab11a-regulate-intercellular-communications-between-neural-cells-via-tunneling-nanotubes
#6
Hui Zhu, Chengbin Xue, Xi Xu, Yibing Guo, Xiaohong Li, Jingjing Lu, Shaoqing Ju, Yongjun Wang, Zheng Cao, Xiaosong Gu
Tunneling nanotubes (TNTs) are F-actin-based membrane tubes, and can form between cultured cells and within vital tissues. TNTs mediate intercellular communications that range from electrical signaling to the transfer of organelles. Following peripheral nerve injury, the orchestrated intercellular communications among neural and non-neural cells are required for effective nerve regeneration. It remains unknown whether TNTs exist between neural cells in the peripheral nerve system and how TNTs affect neural regeneration...
December 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27940993/cdk5-regulation-of-the-grab-mediated-rab8-rab11-cascade-in-axon-outgrowth
#7
Kotaro Furusawa, Akiko Asada, Pamela Urrutia, Christian Gonzalez-Billault, Mitsunori Fukuda, Shin-Ichi Hisanaga
Neurons communicate with each other through their axons and dendrites. However, a full characterization of the molecular mechanisms involved in axon and dendrite formation is still incomplete. Neurite outgrowth requires the supply of membrane components for surface expansion. Two membrane sources for axon outgrowth are suggested, Golgi secretary vesicles and endocytic recycling endosomes. In non-neuronal cells, trafficking of secretary vesicles from Golgi is regulated by Rab8, a member of Rab small GTPases, and that of recycling endosomes is by Rab11, another member of Rabs...
December 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27529348/small-gtpases-rab8a-and-rab11a-are-dispensable-for-rhodopsin-transport-in-mouse-photoreceptors
#8
Guoxin Ying, Cecilia D Gerstner, Jeanne M Frederick, Sanford L Boye, William W Hauswirth, Wolfgang Baehr
Rab11a and Rab8a are ubiquitous small GTPases shown as required for rhodopsin transport in Xenopus laevis and zebrafish photoreceptors by dominant negative (dn) disruption of function. Here, we generated retina-specific Rab11a (retRab11a) and Rab8a (retRab8a) single and double knockout mice to explore the consequences in mouse photoreceptors. Rhodopsin and other outer segment (OS) membrane proteins targeted correctly to OS and electroretinogram (ERG) responses in all three mutant mouse lines were indistinguishable from wild-type (WT)...
2016: PloS One
https://www.readbyqxmd.com/read/27528609/mical3-flavoprotein-monooxygenase-forms-a-complex-with-centralspindlin-and-regulates-cytokinesis
#9
Qingyang Liu, Fan Liu, Ka Lou Yu, Roderick Tas, Ilya Grigoriev, Sanne Remmelzwaal, Andrea Serra-Marques, Lukas C Kapitein, Albert J R Heck, Anna Akhmanova
During cytokinesis, the antiparallel array of microtubules forming the central spindle organizes the midbody, a structure that anchors the ingressed cleavage furrow and guides the assembly of abscission machinery. Here, we identified a role for the flavoprotein monooxygenase MICAL3, an actin disassembly factor, in organizing midbody-associated protein complexes. By combining cell biological assays with cross-linking mass spectrometry, we show that MICAL3 is recruited to the central spindle and the midbody through a direct interaction with the centralspindlin component MKLP1...
September 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27494456/c9orf72-is-a-gdp-gtp-exchange-factor-for-rab8-and-rab39-and-regulates-autophagy
#10
Camille Corbier, Chantal Sellier
Amyotrophic Lateral Sclerosis and Frontotemporal Dementia (ALS-FTD) are devastating neurodegenerative disease affecting motoneurons from the spinal chord and neurons from the frontal and temporal cortex, respectively. The most common genetic cause for ALS-FTD is an expansion of GGGGCC repeats within the first intron of the C9ORF72 gene. However, little is known on the function of C9ORF72. Recently, other and we found that C9ORF72 forms a stable complex with the SMCR8 and WDR41 proteins. This complex acts as a GDP/GTP exchange factor for the small RAB GTPases Rab8a and Rab39b...
August 5, 2016: Small GTPases
https://www.readbyqxmd.com/read/27336832/protease-resistant-and-cell-permeable-double-stapled-peptides-targeting-the-rab8a-gtpase
#11
Philipp M Cromm, Jochen Spiegel, Philipp Küchler, Laura Dietrich, Julia Kriegesmann, Mathias Wendt, Roger S Goody, Herbert Waldmann, Tom N Grossmann
Small GTPases comprise a family of highly relevant targets in chemical biology and medicinal chemistry research and have been considered "undruggable" due to the persisting lack of effective synthetic modulators and suitable binding pockets. As molecular switches, small GTPases control a multitude of pivotal cellular functions, and their dysregulation is associated with many human diseases such as various forms of cancer. Rab-GTPases represent the largest subfamily of small GTPases and are master regulators of vesicular transport interacting with various proteins via flat and extensive protein-protein interactions (PPIs)...
August 19, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27307439/disruption-of-the-ampk-tbc1d1-nexus-increases-lipogenic-gene-expression-and-causes-obesity-in-mice-via-promoting-igf1-secretion
#12
Liang Chen, Qiaoli Chen, Bingxian Xie, Chao Quan, Yang Sheng, Sangsang Zhu, Ping Rong, Shuilian Zhou, Kei Sakamoto, Carol MacKintosh, Hong Yu Wang, Shuai Chen
Tre-2/USP6, BUB2, cdc16 domain family member 1 (the TBC domain is the GTPase activating protein domain) (TBC1D1) is a Rab GTPase activating protein that is phosphorylated on Ser(231) by the AMP-activated protein kinase (AMPK) in response to intracellular energy stress. However, the in vivo role and importance of this phosphorylation event remains unknown. To address this question, we generated a mouse model harboring a TBC1D1(Ser231Ala) knockin (KI) mutation and found that the KI mice developed obesity on a normal chow diet...
June 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27142493/rab-and-rho-gtpases-regulate-intestinal-crypt-cell-homeostasis-and-enterocyte-function
#13
Xiao Zhang, Nan Gao
Recent human and mouse genetic studies have highlighted important contributions of several small GTPases, in particular Rab8a, (1) Cdc42, (2-4) and Rab11a, (5-8) to the proper morphogenesis and function of the mature intestinal epithelia. Additional insights about the involvement of these factors in maintaining intestinal stem cell homeostasis have also been obtained. (9,10) These studies suggest a conserved vesicular and membrane trafficking program utilized by the gastrointestinal tissue to support the rapid epithelial cell turnover and the highly sophisticated physiology of mature epithelial cells...
April 2, 2016: Small GTPases
https://www.readbyqxmd.com/read/27122963/molecular-studies-of-phenotype-variation-in-canine-rpgr-xlpra1
#14
Tatyana Appelbaum, Doreen Becker, Evelyn Santana, Gustavo D Aguirre
PURPOSE: Canine X-linked progressive retinal atrophy 1 (XLPRA1) caused by a mutation in retinitis pigmentosa (RP) GTPase regulator (RPGR) exon ORF15 showed significant variability in disease onset in a colony of dogs that all inherited the same mutant X chromosome. Defective protein trafficking has been detected in XLPRA1 before any discernible degeneration of the photoreceptors. We hypothesized that the severity of the photoreceptor degeneration in affected dogs may be associated with defects in genes involved in ciliary trafficking...
2016: Molecular Vision
https://www.readbyqxmd.com/read/26963025/insulin-degrading-enzyme-secretion-from-astrocytes-is-mediated-by-an-autophagy-based-unconventional-secretory-pathway-in-alzheimer-disease
#15
Sung Min Son, Moon-Yong Cha, Heesun Choi, Seokjo Kang, Hyunjung Choi, Myung-Shik Lee, Sun Ah Park, Inhee Mook-Jung
The secretion of proteins that lack a signal sequence to the extracellular milieu is regulated by their transition through the unconventional secretory pathway. IDE (insulin-degrading enzyme) is one of the major proteases of amyloid beta peptide (Aβ), a presumed causative molecule in Alzheimer disease (AD) pathogenesis. IDE acts in the extracellular space despite having no signal sequence, but the underlying mechanism of IDE secretion extracellularly is still unknown. In this study, we found that IDE levels were reduced in the cerebrospinal fluid (CSF) of patients with AD and in pathology-bearing AD-model mice...
May 3, 2016: Autophagy
https://www.readbyqxmd.com/read/26807810/endoplasmic-reticulum-resident-rab8a-gtpase-is-involved-in-phagocytosis-in-the-protozoan-parasite-entamoeba-histolytica
#16
Yuki Hanadate, Yumiko Saito-Nakano, Kumiko Nakada-Tsukui, Tomoyoshi Nozaki
Phagocytosis is indispensable for the pathogenesis of the intestinal protozoan parasite Entamoeba histolytica. Here, we showed that in E. histolytica Rab8A, which is generally involved in trafficking from the trans-Golgi network to the plasma membrane in other organisms but was previously identified in phagosomes of the amoeba in the proteomic analysis, primarily resides in the endoplasmic reticulum (ER) and participates in phagocytosis. We demonstrated that down-regulation of EhRab8A by small antisense RNA-mediated transcriptional gene silencing remarkably reduced adherence and phagocytosis of erythrocytes, bacteria and carboxylated latex beads...
October 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/26471730/phosphoproteomic-screening-identifies-rab-gtpases-as-novel-downstream-targets-of-pink1
#17
Yu-Chiang Lai, Chandana Kondapalli, Ronny Lehneck, James B Procter, Brian D Dill, Helen I Woodroof, Robert Gourlay, Mark Peggie, Thomas J Macartney, Olga Corti, Jean-Christophe Corvol, David G Campbell, Aymelt Itzen, Matthias Trost, Miratul Mk Muqit
Mutations in the PTEN-induced kinase 1 (PINK1) are causative of autosomal recessive Parkinson's disease (PD). We have previously reported that PINK1 is activated by mitochondrial depolarisation and phosphorylates serine 65 (Ser(65)) of the ubiquitin ligase Parkin and ubiquitin to stimulate Parkin E3 ligase activity. Here, we have employed quantitative phosphoproteomics to search for novel PINK1-dependent phosphorylation targets in HEK (human embryonic kidney) 293 cells stimulated by mitochondrial depolarisation...
November 12, 2015: EMBO Journal
https://www.readbyqxmd.com/read/26372645/adap2-is-an-interferon-stimulated-gene-that-restricts-rna-virus-entry
#18
Qian Shu, Nicholas J Lennemann, Saumendra N Sarkar, Yoel Sadovsky, Carolyn B Coyne
Interferon stimulated genes (ISGs) target viruses at various stages of their infectious life cycles, including at the earliest stage of viral entry. Here we identify ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2) as a gene upregulated by type I IFN treatment in a STAT1-dependent manner. ADAP2 functions as a GTPase-activating protein (GAP) for Arf6 and binds to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and PI(3,4)P2. We show that overexpression of ADAP2 suppresses dengue virus (DENV) and vesicular stomatitis virus (VSV) infection in an Arf6 GAP activity-dependent manner, while exerting no effect on coxsackievirus B (CVB) or Sendai virus (SeV) replication...
September 2015: PLoS Pathogens
https://www.readbyqxmd.com/read/26209634/small-gtpase-rab2b-and-its-specific-binding-protein-golgi-associated-rab2b-interactor-like-4-gari-l4-regulate-golgi-morphology
#19
Megumi Aizawa, Mitsunori Fukuda
Rab small GTPases are crucial regulators of the membrane traffic that maintains organelle identity and morphology. Several Rab isoforms are present in the Golgi, and it has been suggested that they regulate the compacted morphology of the Golgi in mammalian cells. However, the functional relationships among the Golgi-resident Rabs, e.g. whether they are functionally redundant or different, are poorly understood. In this study, we used specific siRNAs to perform genome-wide screening for human Rabs that are involved in Golgi morphology in HeLa-S3 cells...
September 4, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26015543/rab8a-vesicles-regulate-wnt-ligand-delivery-and-paneth-cell-maturation-at-the-intestinal-stem-cell-niche
#20
Soumyashree Das, Shiyan Yu, Ryotaro Sakamori, Pavan Vedula, Qiang Feng, Juan Flores, Andrew Hoffman, Jiang Fu, Ewa Stypulkowski, Alexis Rodriguez, Radek Dobrowolski, Akihiro Harada, Wei Hsu, Edward M Bonder, Michael P Verzi, Nan Gao
Communication between stem and niche supporting cells maintains the homeostasis of adult tissues. Wnt signaling is a crucial regulator of the stem cell niche, but the mechanism that governs Wnt ligand delivery in this compartment has not been fully investigated. We identified that Wnt secretion is partly dependent on Rab8a-mediated anterograde transport of Gpr177 (wntless), a Wnt-specific transmembrane transporter. Gpr177 binds to Rab8a, depletion of which compromises Gpr177 traffic, thereby weakening the secretion of multiple Wnts...
June 15, 2015: Development
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