Tropomodulin3 is a novel Akt2 effector regulating insulin-stimulated GLUT4 exocytosis through cortical actin remodeling
Copyright policy )Tropomodulin3 is a novel Akt2 effector regulating insulin-stimulated GLUT4 exocytosis through cortical actin remodeling
AbstractAkt2 and its downstream effectors mediate insulin-stimulated GLUT4-storage vesicle (GSV) translocation and fusion with the plasma membrane (PM). Using mass spectrometry, we identify actin-capping protein Tropomodulin 3 (Tmod3) as an Akt2-interacting partner in 3T3-L1 adipocytes. We demonstrate that Tmod3 is phosphorylated at Ser71 on insulin-stimulated Akt2 activation, and Ser71 phosphorylation is required for insulin-stimulated GLUT4 PM insertion and glucose uptake. Phosphorylated Tmod3 regulates insulin-induced actin remodelling, an essential step for GSV fusion with the PM. Furthermore, the interaction of Tmod3 with its cognate tropomyosin partner, Tm5NM1 is necessary for GSV exocytosis and glucose uptake. Together these results establish Tmod3 as a novel Akt2 effector that mediates insulin-induced cortical actin remodelling and subsequent GLUT4 membrane insertion. Our findings suggest that defects in cytoskeletal remodelling may contribute to impaired GLUT4 exocytosis and glucose uptake.
- Agency for Science, Technology and Research Singapore
- National University of Singapore Singapore
- UNSW Sydney Australia
- Seoul National University Korea (Republic of)
- Chinese Academy of Sciences China (People's Republic of)
Male, translocation, Mice, actin capping protein, Adipocytes, Insulin, animal, glucose, Phosphorylation, membrane, mass spectrometry, Glucose Transporter Type 4, tropomodulin, actin binding protein, unclassified drug, SLC2A4 protein, exocytosis, actin, signal transduction, Tropomodulin, chemical reaction, Blood Platelets, insulin, cross linking, TMOD3 protein, actin filament, latrunculin B, adipocyte, Article, Exocytosis, proteomics, F actin, 3T3-L1 Cells, glucose transporter 4, 616, Animals, Humans, human, protein interaction, mouse, human cell, Cell Membrane, Lentivirus, glucose transport, AKT2 protein, 3T3 cell line, Actins, protein phosphorylation, Mice, Inbred C57BL, Glucose, Microscopy, Fluorescence, G actin, protein kinase B beta, protein kinase B, cells and cell components, tropomodulin 3, numerical model, protein, Proto-Oncogene Proteins c-akt
Male, translocation, Mice, actin capping protein, Adipocytes, Insulin, animal, glucose, Phosphorylation, membrane, mass spectrometry, Glucose Transporter Type 4, tropomodulin, actin binding protein, unclassified drug, SLC2A4 protein, exocytosis, actin, signal transduction, Tropomodulin, chemical reaction, Blood Platelets, insulin, cross linking, TMOD3 protein, actin filament, latrunculin B, adipocyte, Article, Exocytosis, proteomics, F actin, 3T3-L1 Cells, glucose transporter 4, 616, Animals, Humans, human, protein interaction, mouse, human cell, Cell Membrane, Lentivirus, glucose transport, AKT2 protein, 3T3 cell line, Actins, protein phosphorylation, Mice, Inbred C57BL, Glucose, Microscopy, Fluorescence, G actin, protein kinase B beta, protein kinase B, cells and cell components, tropomodulin 3, numerical model, protein, Proto-Oncogene Proteins c-akt
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).82 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!