Premium
Molecular Basis of Insulin‐Responsive GLUT4 Trafficking Systems Revealed by Single Molecule Imaging
Author(s) -
Hatakeyama Hiroyasu,
Kanzaki Makoto
Publication year - 2011
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2011.01279.x
Subject(s) - glut4 , retromer , biology , microbiology and biotechnology , glucose transporter , insulin , endosome , golgi apparatus , insulin resistance , intracellular , endocrinology , endoplasmic reticulum
Development of a ‘static retention’ property of GLUT4, the insulin‐responsive glucose transporter, has emerged as being essential for achieving its maximal insulin‐induced surface exposure. Herein, employing quantum‐dot‐based nanometrology of intracellular GLUT4 behavior, we reveal the molecular basis of its systematization endowed upon adipogenic differentiation of 3T3L1 cells. Specifically, (i) the endosomes‐to‐ trans ‐Golgi network (TGN) retrieval system specialized for GLUT4 develops in response to sortilin expression, which requires an intricately balanced interplay among retromers, golgin‐97 and syntaxin‐6, the housekeeping vesicle trafficking machinery. (ii) The Golgin‐97‐localizing subdomain of the differentiated TGN apparently serves as an intermediate transit route by which GLUT4 can further proceed to the stationary GLUT4 storage compartment. (iii) AS160/Tbc1d4 then renders the ‘static retention’ property insulin responsive, i.e. insulin liberates GLUT4 from the static state only in the presence of functional AS160/Tbc1d4. (iv) Moreover, sortilin malfunction and the resulting GLUT4 sorting defects along with retarded TGN function might be etiologically related to insulin resistance. Together, these observations provide a conceptual framework for understanding maturation/retardation of the insulin‐responsive GLUT4 trafficking system that relies on the specialized subdomain of differentiated TGN.