1. Complexin-2 redistributes to the membrane of muscle cells in response to insulin and contributes to GLUT4 translocation.
- Author
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Pavarotti MA, Tokarz V, Frendo-Cumbo S, Bilan PJ, Liu Z, Zanni-Ruiz E, Mayorga LS, and Klip A
- Subjects
- Adaptor Proteins, Vesicular Transport genetics, Animals, Cell Membrane drug effects, Cell Membrane metabolism, Cells, Cultured, Glucose Transporter Type 4 genetics, Insulin genetics, Insulin metabolism, Muscle, Skeletal cytology, Myoblasts drug effects, Nerve Tissue Proteins genetics, Protein Transport drug effects, Proto-Oncogene Proteins c-akt metabolism, Rats, Signal Transduction, rac1 GTP-Binding Protein metabolism, Adaptor Proteins, Vesicular Transport metabolism, Glucose Transporter Type 4 metabolism, Insulin pharmacology, Myoblasts metabolism, Nerve Tissue Proteins metabolism
- Abstract
Insulin stimulates glucose uptake in muscle cells by rapidly redistributing vesicles containing GLUT4 glucose transporters from intracellular compartments to the plasma membrane (PM). GLUT4 vesicle fusion requires the formation of SNARE complexes between vesicular VAMP and PM syntaxin4 and SNAP23. SNARE accessory proteins usually regulate vesicle fusion processes. Complexins aide in neuro-secretory vesicle-membrane fusion by stabilizing trans-SNARE complexes but their participation in GLUT4 vesicle fusion is unknown. We report that complexin-2 is expressed and homogeneously distributed in L6 rat skeletal muscle cells. Upon insulin stimulation, a cohort of complexin-2 redistributes to the PM. Complexin-2 knockdown markedly inhibited GLUT4 translocation without affecting proximal insulin signalling of Akt/PKB phosphorylation and actin fiber remodelling. Similarly, complexin-2 overexpression decreased maximal GLUT4 translocation suggesting that the concentration of complexin-2 is finely tuned to vesicle fusion. These findings reveal an insulin-dependent regulation of GLUT4 insertion into the PM involving complexin-2., (© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
- Published
- 2021
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