Abstract
The facilitative glucose transporter type 4 (GLUT4) is expressed in adipose and muscle and plays a vital role in whole body glucose homeostasis. In the absence of insulin, only ~1% of cellular GLUT4 is present at the plasma membrane, with the vast majority localizing to intracellular organelles. GLUT4 is retained intracellularly by continuous trafficking through two inter-related cycles. GLUT4 passes through recycling endosomes, the trans Golgi network and an insulin-sensitive intracellular compartment, termed GLUT4-storage vesicles or GSVs. It is from GSVs that GLUT4 is mobilized to the cell surface in response to insulin, where it increases the rate of glucose uptake into the cell. As with many physiological responses to external stimuli, this regulated trafficking event involves multiple posttranslational modifications. This review outlines the roles of posttranslational modifications of GLUT4 on its function and insulin-regulated trafficking.
Highlights
Glucose is one of the most important energy sources for cells and is one of only three monosaccharides that are absorbed directly into the bloodstream
These vesicles are sequestered ( ) within the cell under basal conditions. This could be mediated by Tether containing UBX domain (TUG), which interacts with both glucose transporter type 4 (GLUT4) in GLUT4 storage vesicles (GSVs) and the Golgi matrix protein, Golgin-160
The reason for sequestering GLUT4 into GSVs is to create a pool of GLUT4 that is responsive to insulin
Summary
Glucose is one of the most important energy sources for cells and is one of only three monosaccharides that are absorbed directly into the bloodstream. The dark grey bar indicates the region thought to interact with the Tether containing UBX domain (TUG); the specific amino acids involved are currently unknown. These vesicles are sequestered ( ) within the cell under basal conditions This could be mediated by Tether containing UBX domain (TUG), which interacts with both GLUT4 in GSVs and the Golgi matrix protein, Golgin-160. Insulin stimulation releases GSVs from storage, and they are transported ( ) to the plasma membrane. GLUT4 is endocytosed ( ) and transported to the endosomal system for recycling ( ) This is either to the plasma membrane (if insulin is still present) or back to GSVs (if insulin is absent). The general endosomal recycling system serves to efficiently internalize GLUT4 cycling through early endosomes From this cycle, GLUT4 enters a more specialized trafficking pathway that renders it insulin-sensitive. We will follow the journey of a GLUT4 molecule as it travels through multiple subcellular compartments (Figure 2), discussing evidence for post-translational modifications and the effects these have on localization and function
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