Update on GLUT4 Vesicle Traffic: A Cornerstone of Insulin Action

Javier R Jaldin-Fincati; Martin Pavarotti; Scott Frendo-Cumbo; Philip J Bilan; Amira Klip

doi:10.1016/j.tem.2017.05.002

Update on GLUT4 Vesicle Traffic: A Cornerstone of Insulin Action

Trends Endocrinol Metab. 2017 Aug;28(8):597-611. doi: 10.1016/j.tem.2017.05.002. Epub 2017 Jun 8.

Authors

Javier R Jaldin-Fincati¹, Martin Pavarotti², Scott Frendo-Cumbo³, Philip J Bilan¹, Amira Klip⁴

Affiliations

¹ Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5J 2L4, Canada.
² Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5J 2L4, Canada; IHEM, Universidad Nacional de Cuyo, CONICET, Mendoza 5500, Argentina.
³ Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5J 2L4, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
⁴ Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5J 2L4, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: amira@sickkids.ca.

PMID: 28602209
DOI: 10.1016/j.tem.2017.05.002

Abstract

Glucose transport is rate limiting for dietary glucose utilization by muscle and fat. The glucose transporter GLUT4 is dynamically sorted and retained intracellularly and redistributes to the plasma membrane (PM) by insulin-regulated vesicular traffic, or 'GLUT4 translocation'. Here we emphasize recent findings in GLUT4 translocation research. The application of total internal reflection fluorescence microscopy (TIRFM) has increased our understanding of insulin-regulated events beneath the PM, such as vesicle tethering and membrane fusion. We describe recent findings on Akt-targeted Rab GTPase-activating proteins (GAPs) (TBC1D1, TBC1D4, TBC1D13) and downstream Rab GTPases (Rab8a, Rab10, Rab13, Rab14, and their effectors) along with the input of Rac1 and actin filaments, molecular motors [myosinVa (MyoVa), myosin1c (Myo1c), myosinIIA (MyoIIA)], and membrane fusion regulators (syntaxin4, munc18c, Doc2b). Collectively these findings reveal novel events in insulin-regulated GLUT4 traffic.

Keywords: GLUT4; Rab GTPases; actin cytoskeleton; insulin signaling; membrane fusion; vesicle traffic.

Publication types

Review

MeSH terms

Animals
Cytoplasmic Vesicles / drug effects
Cytoplasmic Vesicles / metabolism*
Glucose Transporter Type 4 / metabolism*
Humans
Insulin / pharmacology
Insulin / physiology*
Mice
Protein Transport / drug effects

Substances

Glucose Transporter Type 4
Insulin