GLUT4 dispersal at the plasma membrane of adipocytes: a super-resolved journey

In adipose tissue, insulin stimulates glucose uptake by mediating the translocation of GLUT4 from intracellular vesicles to the plasma membrane. In 2010, insulin was revealed to also have a fundamental impact on the spatial distribution of GLUT4 within the plasma membrane, with the existence of two...

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Bibliographic Details
Published in:Bioscience reports 2023-10, Vol.43 (10), p.1
Main Authors: Geiser, Angéline, Foylan, Shannan, Tinning, Peter W, Bryant, Nia J, Gould, Gwyn W
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 4-kinase
Adipocytes
Adipose tissue
Aperture
Biophysics
Cell Membranes, Excitation & Transport
Cell surface
Clusters
Diabetes
Diabetes & Metabolic Disorders
Dispersal
Dispersion
Exocytosis
Glucose
Insulin
Insulin resistance
Kinases
Light
Localization
Membrane vesicles
Membranes
Microscopes
Microscopy
Monomers
Plasma
Proteins
Review
Spatial distribution
Translocation
Vesicle fusion
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Summary:In adipose tissue, insulin stimulates glucose uptake by mediating the translocation of GLUT4 from intracellular vesicles to the plasma membrane. In 2010, insulin was revealed to also have a fundamental impact on the spatial distribution of GLUT4 within the plasma membrane, with the existence of two GLUT4 populations at the plasma membrane being defined: (1) as stationary clusters and (2) as diffusible monomers. In this model, in the absence of insulin, plasma membrane-fused GLUT4 are found to behave as clusters. These clusters are thought to arise from exocytic events that retain GLUT4 at their fusion sites; this has been proposed to function as an intermediate hub between GLUT4 exocytosis and re-internalisation. By contrast, insulin stimulation induces the dispersal of GLUT4 clusters into monomers and favours a distinct type of GLUT4-vesicle fusion event, known as fusion-with-release exocytosis. Here, we review how super-resolution microscopy approaches have allowed investigation of the characteristics of plasma membrane-fused GLUT4 and further discuss regulatory step(s) involved in the GLUT4 dispersal machinery, introducing the scaffold protein EFR3 which facilitates localisation of phosphatidylinositol 4-kinase type IIIα (PI4KIIIα) to the cell surface. We consider how dispersal may be linked to the control of transporter activity, consider whether macro-organisation may be a widely used phenomenon to control proteins within the plasma membrane, and speculate on the origin of different forms of GLUT4-vesicle exocytosis.
ISSN:0144-8463
1573-4935
DOI:10.1042/BSR20230946