Open AccessComplexin-2 redistributes to the membrane of muscle cells in response to insulin and contributes to GLUT4 translocation
Author(s) -
Martín Pavarotti,
Victoria L. Tokarz,
Scott FrendoCumbo,
Philip J. Bilan,
Liu Zhi,
Emilia Zanni-Ruiz,
Luis S. Mayorga,
Amira Klip
Publication year - 2021
Publication title -
biochemical journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.706
H-Index - 265
eISSN - 1470-8728
pISSN - 0264-6021
DOI - 10.1042/bcj20200542
Subject(s) - glut4 , microbiology and biotechnology , vesicle fusion , vesicle , biology , vesicular transport protein , lipid bilayer fusion , kiss and run fusion , phosphorylation , glucose transporter , insulin , synaptic vesicle , biochemistry , endocrinology , membrane
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.