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10.1091/mbc.E15-05-0319

http://scihub22266oqcxt.onion/10.1091/mbc.E15-05-0319
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suck abstract from ncbi


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pmid26538022
      Mol+Biol+Cell 2016 ; 27 (1 ): 75-89
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  • A complex of Rab13 with MICAL-L2 and ?-actinin-4 is essential for insulin-dependent GLUT4 exocytosis #MMPMID26538022
  • Sun Y ; Jaldin-Fincati J ; Liu Z ; Bilan PJ ; Klip A
  • Mol Biol Cell 2016[Jan]; 27 (1 ): 75-89 PMID26538022 show ga
  • Insulin promotes glucose uptake into skeletal muscle through recruitment of glucose transporter 4 (GLUT4) to the plasma membrane. Rab GTPases are molecular switches mobilizing intracellular vesicles, and Rab13 is necessary for insulin-regulated GLUT4-vesicle exocytic translocation in muscle cells. We show that Rab13 engages the scaffold protein MICAL-L2 in this process. RNA interference-mediated knockdown of MICAL-L2 or truncated MICAL-L2 (MICAL-L2-CT) impaired insulin-stimulated GLUT4 translocation. Insulin increased Rab13 binding to MICAL-L2, assessed by pull down and colocalization under confocal fluorescence and structured illumination microscopies. Association was also visualized at the cell periphery using TIRF microscopy. Insulin further increased binding of MICAL-L2 to ?-actinin-4 (ACTN4), a protein involved in GLUT4 translocation. Rab13, MICAL-L2, and ACTN4 formed an insulin-dependent complex assessed by pull down and confocal fluorescence imaging. Of note, GLUT4 associated with the complex in response to insulin, requiring the ACTN4-binding domain in MICAL-L2. This was demonstrated by pull down with distinct fragments of MICAL-L2 and confocal and structured illumination microscopies. Finally, expression of MICAL-L2-CT abrogated the insulin-dependent colocalization of Rab13 with ACTN4 or Rab13 with GLUT4. Our findings suggest that MICAL-L2 is an effector of insulin-activated Rab13, which links to GLUT4 through ACTN4, localizing GLUT4 vesicles at the muscle cell periphery to enable their fusion with the membrane.
  • |Actinin/*metabolism [MESH]
  • |Animals [MESH]
  • |Cell Line [MESH]
  • |Cell Membrane/metabolism [MESH]
  • |Exocytosis/physiology [MESH]
  • |GTP Phosphohydrolases/*metabolism [MESH]
  • |Glucose Transporter Type 4/*metabolism [MESH]
  • |Humans [MESH]
  • |Insulin/metabolism/pharmacology [MESH]
  • |Microfilament Proteins/*metabolism [MESH]
  • |Muscle Cells/metabolism [MESH]
  • |Protein Binding [MESH]
  • |Protein Transport [MESH]
  • |Rats [MESH]
  • |Signal Transduction [MESH]
  • |Tight Junctions/metabolism [MESH]


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