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.
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High protein levels of protein kinase C confer a survival advantage in many cancers, including pancreatic cancer. In this issue, Tovell and Newton (pp. 341–355) review the mechanisms controlling the stability of protein kinase C, focusing on negative regulation by the phosphatase PHLPP as a potential strategy to restore protein levels of the kinase. Image provided by Hannah Tovell and was created with BioRender.com.
Complexin-2 redistributes to the membrane of muscle cells in response to insulin and contributes to GLUT4 translocation
Martin Alejandro Pavarotti, Victoria Tokarz, Scott Frendo-Cumbo, Philip J. Bilan, Zhi Liu, Emilia Zanni-Ruiz, Luis Segundo Mayorga, Amira Klip; Complexin-2 redistributes to the membrane of muscle cells in response to insulin and contributes to GLUT4 translocation. Biochem J 29 January 2021; 478 (2): 407–422. doi: https://doi.org/10.1042/BCJ20200542
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