Glucose entry into muscle cells is precisely regulated by insulin, through recruitment of GLUT4 (glucose transporter-4) to the membrane of muscle and fat cells. Work done over more than two decades has contributed to mapping the insulin signalling and GLUT4 vesicle trafficking events underpinning this response. In spite of this intensive scientific research, there are outstanding questions that continue to challenge us today. The present review summarizes the knowledge in the field, with emphasis on the latest breakthroughs in insulin signalling at the level of AS160 (Akt substrate of 160 kDa), TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) and their target Rab proteins; in vesicle trafficking at the level of vesicle mobilization, tethering, docking and fusion with the membrane; and in the participation of the cytoskeleton to achieve optimal temporal and spatial location of insulin-derived signals and GLUT4 vesicles.
- actin dynamics
- glucose transporter 4 (GLUT4)
- insulin signalling
- muscle cells
- vesicle traffic
Abbreviations: ACTN4, α-actinin 4; aPKC, atypical protein kinase C; AS160, Akt substrate of 160 kDa; GAP, GTPase-activating protein; GFP, green fluorescent protein; GLUT4, glucose transporter 4; GSV, GLUT4-storage vesicle; IGF, insulin-like growth factor; IRAP, insulin-regulated aminopeptidase; IRS, insulin receptor substrate; NSF, N-ethylmaleimide-sensitive factor; PH, pleckstrin homology; PI3K, phosphoinositide 3-kinase; PIKfyve, FYVE-domain containing PtdIns3P 5-kinase; PKB, protein kinase B; PKC, protein kinase C; PM, plasma membrane; PTEN, phosphatase and tensin homologue deleted on chromosome 10; RE, recycling endosome; SC, specialized or storage compartment; SHIP2, Src homology 2-containing inositol phosphatase-2; siRNA, small interfering RNA; SM, Sec1p/Munc18; SNAP, soluble NSF-attachment protein; TBC1D1, tre-2/USP6, BUB2, cdc16 domain family member 1; TfR, transferrin receptor; TGN, trans-Golgi network; TIRF, total internal reflection fluorescence; t-SNARE, target SNARE; TUG, tether containing UBX domain for GLUT4; VAMP2, vesicle-associated membrane protein 2; v-SNARE, vesicular soluble N-ethylmaleimide-sensitive factor-attachment protein receptor; WASP, Wiskott–Aldrich syndrome protein
- © The Authors Journal compilation © 2008 Biochemical Society