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. 2017 Nov 20;8:329. doi: 10.3389/fendo.2017.00329

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Copyright © 2017 Tunduguru and Thurmond.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Exocytosis to endocytosis, and back. Schematic model showing actin filament and microtubule-dependent exocytosis of glucose transporter-4 (GLUT4) (leftmost pathway), and clathrin-mediated GLUT4 endocytosis (rightmost pathway) in skeletal muscle and adipose cells. GLUT4 present at the plasma membrane (PM) is endocytosed in a Clathrin-dependent manner requiring the adaptor protein-2 (AP2) adapter and the GTPase Dynamin. Rab GTPases 4 and 5 are implicated in the distal step to generate recycling endosomes carrying GLUT4, afterwhich GLUT4 is taken to the trans-Golgi network (TGN) via Rab11 or possibly back to a GLUT4 storage vesicle (GSV) pool via Rab4/11. Exocytosis of GLUT4 in GSVs that also carry the vesicle SNARE [vesicle associated membrane protein-2 (VAMP2)] from the TGN requires Rabs8/10/14; Rab31 counteracts this action. GSVs travel along microtubules via kinesins (KIF5B) and actin filaments (via RalA and MYO1C), bringing GSVs into close proximity with the PM t-SNARE proteins [Syntaxin 4 (STX4) and synaptosomal-associated protein-23 (SNAP-23)].