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https://www.readbyqxmd.com/read/28108651/roflumilast-and-aquaporin-2-regulation-in-rat-renal-inner-medullary-collecting-duct
#1
Ezigbobiara N Umejiego, Yanhua Wang, Mark A Knepper, Chung-Lin Chou
Roflumilast is a cyclic nucleotide phosphodiesterase inhibitor that is FDA-approved for treatment of chronic obstructive pulmonary disease. With a view toward possible use for treatment of patients with X-linked nephrogenic diabetes insipidus (NDI) due to hemizygous mutations in the V2 vasopressin receptor, this study sought to determine the effect of roflumilast on aquaporin-2 (AQP2) phosphorylation, AQP2 trafficking, and water permeability in the rat inner medullary collecting duct (IMCD). In the presence of the vasopressin analog dDAVP (0...
January 2017: Physiological Reports
https://www.readbyqxmd.com/read/28108526/vaps-and-acbd5-tether-peroxisomes-to-the-er-for-peroxisome-maintenance-and-lipid-homeostasis
#2
Rong Hua, Derrick Cheng, Étienne Coyaud, Spencer Freeman, Erminia Di Pietro, Yuqing Wang, Adriano Vissa, Christopher M Yip, Gregory D Fairn, Nancy Braverman, John H Brumell, William S Trimble, Brian Raught, Peter K Kim
Lipid exchange between the endoplasmic reticulum (ER) and peroxisomes is necessary for the synthesis and catabolism of lipids, the trafficking of cholesterol, and peroxisome biogenesis in mammalian cells. However, how lipids are exchanged between these two organelles is not understood. In this study, we report that the ER-resident VAMP-associated proteins A and B (VAPA and VAPB) interact with the peroxisomal membrane protein acyl-CoA binding domain containing 5 (ACBD5) and that this interaction is required to tether the two organelles together, thereby facilitating the lipid exchange between them...
January 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28108259/appls-more-than-just-adiponectin-receptor-binding-proteins
#3
REVIEW
Zhuoying Liu, Ting Xiao, Xiaoyu Peng, Guangdi Li, Fang Hu
APPLs (adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif) are multifunctional adaptor proteins that bind to various membrane receptors, nuclear factors and signaling proteins to regulate many biological activities and processes, such as cell proliferation, chromatin remodeling, endosomal trafficking, cell survival, cell metabolism and apoptosis. APPL1, one of the APPL isoforms, was the first identified protein and interacts directly with adiponectin receptors to mediate adiponectin signaling to enhance lipid oxidation and glucose uptake...
January 17, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28106386/macromolecularly-caged-carbon-nanoparticles-for-intracel-lular-trafficking-via-switchable-photo-luminescence
#4
Santosh K Misra, Indrajit Srivastava, Indu Tripathi, Enrique A Daza, Fatemeh Ostadhossein, Dipanjan Pan
Reversible switching of photoluminescence (PL) of carbon nanoparticles (CNP) can be achieved with counter-ionic macromolecular caging and de-caging at the nanoscale. A negatively charged uncoated, 'bare' CNP with high luminescence loses its PL when positively charged macromolecules are wrapped around its surface. Prepared caged carbons could regain their emission only through interaction with anionic surfactant mole-cules, representing anionic amphiphiles of endocytic membranes. This process could be verified by gel electrophoresis, spectroscopically and in vitro confocal imaging studies...
January 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28104793/rab23-s-genetic-structure-function-and-related-diseases-a-review
#5
Li-Qiang Zheng, Su-Min Chi, Cheng-Xin Li
Rab23, has been proven to play a role in membrane trafficking and protein transport in eukaryotic cells. Rab23 is also a negative regulator of the Sonic hedgehog signaling pathway in an indirect way. The nonsense mutation and loss of protein of Rab23 has been associated with neural tube defect in mice and aberrant expression in various diseases in human such as neural system,breast, visceral and cutaneous tumor. In addition, Rab23 may play joint  roles in autophagosome formation during anti-infection process against  Group A streptococcus...
January 19, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28103577/association-of-rab5-overexpression-in-pancreatic-cancer-with-cancer-progression-and-poor-prognosis-via-e-cadherin-suppression
#6
Takamichi Igarashi, Kenichiro Araki, Takehiko Yokobori, Bolag Altan, Takahiro Yamanaka, Norihiro Ishii, Mariko Tsukagoshi, Akira Watanabe, Norio Kubo, Tadashi Handa, Yasuo Hosouchi, Masahiko Nishiyama, Tetsunari Oyama, Ken Shirabe, Hiroyuki Kuwano
Pancreatic cancer is a common type of cancer with poor prognosis worldwide. Postoperative survival depends on the existence of metastasis. Elucidation of the mechanism underlying cancer progression is important to improve prognosis. The RAS-associated protein RAB5 activates intracellular membrane trafficking, and RAB5 expression is correlated to progression and epithelial mesenchymal transition in various cancers.The expression of RAB5 and E-cadherin in 111 pancreatic cancer samples was investigated by immunohistochemical staining, and the relationship among RAB5 expression, clinicopathological factors, and E-cadherin expression was assessed...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28102838/autophagy-dysregulation-in-danon-disease
#7
Anna Chiara Nascimbeni, Marina Fanin, Corrado Angelini, Marco Sandri
The autophagy-lysosome system is critical for muscle homeostasis and defects in lysosomal function result in a number of inherited muscle diseases, generally referred to as autophagic vacuolar myopathies (AVMs). Among them, Danon Disease (DD) and glycogen storage disease type II (GSDII) are due to primary lysosomal protein defects. DD is characterized by mutations in the lysosome-associated membrane protein 2 (LAMP2) gene. The DD mouse model suggests that inefficient lysosome biogenesis/maturation and impairment of autophagosome-lysosome fusion contribute to the pathogenesis of muscle wasting...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102201/direct-pip2-binding-mediates-stable-oligomer-formation-of-the-serotonin-transporter
#8
Andreas Anderluh, Tina Hofmaier, Enrico Klotzsch, Oliver Kudlacek, Thomas Stockner, Harald H Sitte, Gerhard J Schütz
The human serotonin transporter (hSERT) mediates uptake of serotonin from the synaptic cleft and thereby terminates serotonergic signalling. We have previously found by single-molecule microscopy that SERT forms stable higher-order oligomers of differing stoichiometry at the plasma membrane of living cells. Here, we report that SERT oligomer assembly at the endoplasmic reticulum (ER) membrane follows a dynamic equilibration process, characterized by rapid exchange of subunits between different oligomers, and by a concentration dependence of the degree of oligomerization...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28100664/rab1-interacts-with-golph3-and-controls-golgi-structure-and-contractile-ring-constriction-during-cytokinesis-in-drosophila-melanogaster
#9
Stefano Sechi, Anna Frappaolo, Roberta Fraschini, Luisa Capalbo, Marco Gottardo, Giorgio Belloni, David M Glover, Alan Wainman, Maria Grazia Giansanti
Cytokinesis requires a tight coordination between actomyosin ring constriction and new membrane addition along the ingressing cleavage furrow. However, the molecular mechanisms underlying vesicle trafficking to the equatorial site and how this process is coupled with the dynamics of the contractile apparatus are poorly defined. Here we provide evidence for the requirement of Rab1 during cleavage furrow ingression in cytokinesis. We demonstrate that the gene omelette (omt) encodes the Drosophila orthologue of human Rab1 and is required for successful cytokinesis in both mitotic and meiotic dividing cells of Drosophila melanogaster We show that Rab1 protein colocalizes with the conserved oligomeric Golgi (COG) complex Cog7 subunit and the phosphatidylinositol 4-phosphate effector GOLPH3 at the Golgi stacks...
January 2017: Open Biology
https://www.readbyqxmd.com/read/28098232/crystal-structure-of-sec10-a-subunit-of-the-exocyst-complex
#10
Jianxing Chen, Atsushi Yamagata, Keiko Kubota, Yusuke Sato, Sakurako Goto-Ito, Shuya Fukai
The exocyst complex is a heterooctameric protein complex composed of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84. This complex plays an essential role in trafficking secretory vesicles to the plasma membrane through its interaction with phosphatidylinositol 4,5-bisphosphate and small GTPases. To date, the near-full-length structural information of each subunit has been limited to Exo70, although the C-terminal half structures of Sec6, Sec15 and Exo84 and the structures of the small GTPase-binding domains of Sec3, Sec5 and Exo84 have been reported...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097795/impaired-n-linked-glycosylation-of-uptake-and-efflux-transporters-in-human-nonalcoholic-fatty-liver-disease
#11
John D Clarke, Petr Novak, April D Lake, Rhiannon N Hardwick, Nathan J Cherrington
BACKGROUND & AIMS: N-linked glycosylation of proteins is critical for proper protein folding and trafficking to the plasma membrane. Drug transporters are one class of proteins that have reduced function when glycosylation is impaired. N-linked glycosylation of plasma proteins has also been investigated as a biomarker for several liver diseases, including non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to assess the transcriptomic expression of genes involved in protein processing and glycosylation, and to determine the glycosylation status of key drug transporters during human NAFLD progression...
January 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28096472/myosin-vi-facilitates-connexin-43-gap-junction-accretion
#12
Bennett Waxse, Prabuddha Sengupta, Geoffrey G Hesketh, Jennifer Lippincott-Schwartz, Folma Buss
In this study, we demonstrate myosin VI enrichment at Cx43 gap junctions in heart tissue, primary cardiomyocytes and cell culture models. The loss of myosin VI via siRNA-mediated knock down or isolation of primary cardiac tissue and fibroblasts from the myosin VI-null mouse results in reduced GJ plaque size with a concomitant reduction in intercellular communication as shown by FRAP and a new method of selective calcein administration. Analysis of the molecular role of myosin VI in Cx43 trafficking indicates that myosin VI is dispensable in the delivery of Cx43 to the cell surface and connexon movement in the plasma membrane...
January 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28096465/sequences-within-the-c-terminus-of-the-metabotropic-glutamate-receptor-mglur5-are-responsible-for-inner-nuclear-membrane-localization
#13
Ismail Sergin, Yuh-Jiin I Jong, Steven K Harmon, Vikas Kumar, Karen L O'Malley
Traditionally G-protein coupled receptors (GPCR) are thought to be located on the cell surface where they transmit extracellular signals to the cytoplasm. However recent studies indicate that some GPCRs are also localized to various subcellular compartments such as the nucleus where they appear required for various biological functions. For example, the metabotropic glutamate receptor 5, mGluR5, is concentrated at the inner nuclear membrane (INM) where it mediates Ca2+ changes in the nucleoplasm by coupling with Gq/11...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096376/myosin-driven-transport-network-in-plants
#14
Elizabeth G Kurth, Valera V Peremyslov, Hannah L Turner, Kira S Makarova, Jaime Iranzo, Sergei L Mekhedov, Eugene V Koonin, Valerian V Dolja
We investigate the myosin XI-driven transport network in Arabidopsis using protein-protein interaction, subcellular localization, gene knockout, and bioinformatics analyses. The two major groups of nodes in this network are myosins XI and their membrane-anchored receptors (MyoB) that, together, drive endomembrane trafficking and cytoplasmic streaming in the plant cells. The network shows high node connectivity and is dominated by generalists, with a smaller fraction of more specialized myosins and receptors...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096354/loss-of-get-pathway-orthologs-in-arabidopsis-thaliana-causes-root-hair-growth-defects-and-affects-snare-abundance
#15
Shuping Xing, Dietmar Gerald Mehlhorn, Niklas Wallmeroth, Lisa Yasmin Asseck, Ritwika Kar, Alessa Voss, Philipp Denninger, Vanessa Aphaia Fiona Schmidt, Markus Schwarzländer, York-Dieter Stierhof, Guido Grossmann, Christopher Grefen
Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are key players in cellular trafficking and coordinate vital cellular processes, such as cytokinesis, pathogen defense, and ion transport regulation. With few exceptions, SNAREs are tail-anchored (TA) proteins, bearing a C-terminal hydrophobic domain that is essential for their membrane integration. Recently, the Guided Entry of Tail-anchored proteins (GET) pathway was described in mammalian and yeast cells that serve as a blueprint of TA protein insertion [Schuldiner M, et al...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096328/dynamic-pin-formed-auxin-efflux-carrier-phosphorylation-at-the-plasma-membrane-controls-auxin-efflux-dependent-growth
#16
Benjamin Weller, Melina Zourelidou, Lena Frank, Inês C R Barbosa, Astrid Fastner, Sandra Richter, Gerd Jürgens, Ulrich Z Hammes, Claus Schwechheimer
The directional distribution of the phytohormone auxin is essential for plant development. Directional auxin transport is mediated by the polarly distributed PIN-FORMED (PIN) auxin efflux carriers. We have previously shown that efficient PIN1-mediated auxin efflux requires activation through phosphorylation at the four serines S1-S4 in Arabidopsis thaliana The Brefeldin A (BFA)-sensitive D6 PROTEIN KINASE (D6PK) and the BFA-insensitive PINOID (PID) phosphorylate and activate PIN1 through phosphorylation at all four phosphosites...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096264/adherens-junctions-on-the-move-membrane-trafficking-of-e-cadherin
#17
Lena Brüser, Sven Bogdan
Cadherin-based adherens junctions are conserved structures that mediate epithelial cell-cell adhesion in invertebrates and vertebrates. Despite their pivotal function in epithelial integrity, adherens junctions show a remarkable plasticity that is a prerequisite for tissue architecture and morphogenesis. Epithelial cadherin (E-cadherin) is continuously turned over and undergoes cycles of endocytosis, sorting and recycling back to the plasma membrane. Mammalian cell culture and genetically tractable model systems such as Drosophila have revealed conserved, but also distinct, mechanisms in the regulation of E-cadherin membrane trafficking...
January 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28092406/llfh1-mediated-interaction-between-actin-fringe-and-exocytic-vesicles-is-involved-in-pollen-tube-tip-growth
#18
Shanwei Li, Huaijian Dong, Weike Pei, Chaonan Liu, Sha Zhang, Tiantian Sun, Xiuhua Xue, Haiyun Ren
Pollen tube tip growth is an extreme form of polarized cell growth, which requires polarized exocytosis based on a dynamic actin cytoskeleton. However, the molecular basis for the connection between actin filaments and exocytic vesicles is unclear. Here, we identified a Lilium longiflorum pollen-specific formin (LlFH1) and found that it localized at the apical vesicles and plasma membrane (PM). Overexpression of LlFH1 induced excessive actin cables in the tube tip region, and downregulation of LlFH1 eliminated the actin fringe...
January 16, 2017: New Phytologist
https://www.readbyqxmd.com/read/28090783/probing-the-druggability-of-membrane-bound-rab5-by-molecular-dynamics-simulations
#19
Eileen Edler, Matthias Stein
Rab5 is a small GTPase and a key regulator in early endosomal trafficking. Rab5 and its effectors are involved in a large number of infectious diseases and certain types of cancer. We performed µs atomistic molecular dynamics simulations of inactive and active full-length Rab5 anchored to a complex model bilayer with composition of the early endosome membrane. Direct interactions between the Rab5 G domain and the bilayer were observed. We found two dominant nucleotide-dependent orientations characterised by a different accessibility of the switch regions...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28089266/trpc1-orai1-and-stim1-in-soce-friends-in-tight-spaces
#20
REVIEW
Indu S Ambudkar, Lorena Brito de Souza, Hwei Ling Ong
Store-operated calcium entry (SOCE) is a ubiquitous Ca(2+) entry pathway that is activated in response to depletion of ER-Ca(2+) stores and critically controls the regulation of physiological functions in miscellaneous cell types. The transient receptor potential canonical 1 (TRPC1) is the first member of the TRPC channel subfamily to be identified as a molecular component of SOCE. While TRPC1 has been shown to contribute to SOCE and regulate various functions in many cells, none of the reported TRPC1-mediated currents resembled ICRAC, the highly Ca(2+)-selective store-dependent current first identified in lymphocytes and mast cells...
December 30, 2016: Cell Calcium
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