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. 2022 Feb 11;479(3):445-462.
doi: 10.1042/BCJ20210073.

GLUT4 On the move

Daniel J Fazakerley  1 , Francoise Koumanov  2 , Geoffrey D Holman  3
Affiliations

GLUT4 On the move

Daniel J Fazakerley et al. Biochem J. .

Abstract

Insulin rapidly stimulates GLUT4 translocation and glucose transport in fat and muscle cells. Signals from the occupied insulin receptor are translated into downstream signalling changes in serine/threonine kinases within timescales of seconds, and this is followed by delivery and accumulation of the glucose transporter GLUT4 at the plasma membrane. Kinetic studies have led to realisation that there are distinct phases of this stimulation by insulin. There is a rapid initial burst of GLUT4 delivered to the cell surface from a subcellular reservoir compartment and this is followed by a steady-state level of continuing stimulation in which GLUT4 recycles through a large itinerary of subcellular locations. Here, we provide an overview of the phases of insulin stimulation of GLUT4 translocation and the molecules that are currently considered to activate these trafficking steps. Furthermore, we suggest how use of new experimental approaches together with phospho-proteomic data may help to further identify mechanisms for activation of these trafficking processes.

Keywords: GLUT4; glucose transport; insulin; membrane traffic; membrane trafficking kinetics; signal transduction.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1.
Figure 1.. GLUT4 sequestration and exocytosis.
The schematic diagram represents an extension of the 3-compartment sequestration model [42] and the 4-compartment dynamic-retention model [54,55]). The compartments considered in modelling of kinetics of GLUT4 traffic are the plasma membrane (PM), a sequestered GLUT4 vesicle (GSV) compartment, sorting endosomes (SE) and perinuclear compartments (PNC) and an endosome recycling compartment (ERC). The GSV reservoir is supplied by vesicles from SE and PNC, but the proportion of vesicles supplied by these compartments will vary in different cell types. In basal 3T3-L1 cells ∼80% of the GLUT4 is present in GSV, while 20% of GLUT4 is recycled from SE through ERC to the PM [54]. We suggest here that a retention-catalyst C is responsible for the partitioning and saturation of the sequestered GLUT4 compartment. It is proposed that C catalyses formation of GSV. In addition, C is released from the GSV compartment when insulin signalling leads to vesicle fusion with the PM. The rate constants linking these compartments are: kseq for movements at the saturable step and requiring C; kf for fusion of docked vesicles with the plasma membrane — and associated with desaturation of the GSV compartment and release or recycling of C; krd for reversal of docking without fusion — this step involves vesicles that sample docking sites but do not fuse; krc for recycling of GLUT4 from SE through ERC and to the PM.
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References

    1. Kahn, C.R. (1979) What is the molecular basis for the action of insulin? Trends Biochem. Sci. 4, N263–N266 10.1016/0968-0004(79)90201-9 - DOI
    1. Cushman, S.W. and Wardzala, L.J. (1980) Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane. J. Biol. Chem. 255, 4758–4762 10.1016/S0021-9258(19)85561-8 - DOI - PubMed
    1. Suzuki, K. and Kono, T. (1980) Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site. Proc. Natl Acad. Sci. U.S.A. 77, 2542–2545 10.1073/pnas.77.5.2542 - DOI - PMC - PubMed
    1. James, D.E., Strube, M. and Mueckler, M. (1989) Molecular cloning and characterization of an insulin-regulatable glucose transporter. Nature 338, 83–87 10.1038/338083a0 - DOI - PubMed
    1. Charron, M.J., Brosius, III, F.C., Alper, S.L. and Lodish, H.F. (1989) A glucose transport protein expressed predominately in insulin-responsive tissues. Proc. Natl Acad. Sci. U.S.A. 86, 2535–2539 10.1073/pnas.86.8.2535 - DOI - PMC - PubMed

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