Regulated dynamic subcellular GLUT4 localization revealed by proximal proteome mapping in human muscle cells.

Publisher: Company of Biologists Country of Publication: England NLM ID: 0052457 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-9137 (Electronic) Linking ISSN: 00219533 NLM ISO Abbreviation: J Cell Sci Subsets: MEDLINE

Publication: Cambridge : Company of Biologists
Original Publication: London.

Muscle Cells* ; Proteome* ; Glucose Transporter Type 4*/metabolism; Humans ; AMP-Activated Protein Kinases ; Cell Membrane ; Muscles

Regulation of glucose transport, which is central for control of whole-body metabolism, is determined by the amount of GLUT4 glucose transporter (also known as SLC2A4) in the plasma membrane (PM) of fat and muscle cells. Physiologic signals [such as activated insulin receptor or AMP-activated protein kinase (AMPK)] increase PM GLUT4. Here, we show that the distribution of GLUT4 between the PM and interior of human muscle cells is dynamically maintained, and that AMPK promotes PM redistribution of GLUT4 by regulating exocytosis and endocytosis. Stimulation of exocytosis by AMPK is mediated by Rab10 and the Rab GTPase-activating protein TBC1D4. APEX2 proximity mapping reveals that GLUT4 traverses both PM-proximal and PM-distal compartments in unstimulated muscle cells, further supporting retention of GLUT4 by a constitutive retrieval mechanism. AMPK-stimulated translocation involves GLUT4 redistribution among the same compartments traversed in unstimulated cells, with a significant recruitment of GLUT4 from the Golgi and trans-Golgi network compartments. Our comprehensive proximal protein mapping provides an integrated, high-density, whole-cell accounting of the localization of GLUT4 at a resolution of ∼20 nm that serves as a structural framework for understanding the molecular mechanisms regulating GLUT4 trafficking downstream of different signaling inputs in a physiologically relevant cell type.
Competing Interests: Competing interests T.E.M. declares that this project was partially supported by Pfizer Inc. and has nothing else to declare. M.M. and M.J.B. were employees and shareholders of Pfizer Inc. B.B.Z., K.H., Q.X., J.C., J.G. and L.X. are employees and shareholders of Pfizer Inc. A.R., I.S.P., J.W. and L.Y. declare no competing or financial interests.
(© 2023. Published by The Company of Biologists Ltd.)

Update of: bioRxiv. 2023 Jun 07;:. (PMID: 37333333)

Traffic. 2008 Jul;9(7):1173-90. (PMID: 18435821)
Trends Cell Biol. 2020 Sep;30(9):705-719. (PMID: 32620516)
Nat Genet. 2000 May;25(1):25-9. (PMID: 10802651)
Sci Rep. 2022 Sep 19;12(1):15640. (PMID: 36123369)
Am J Physiol Endocrinol Metab. 2019 Dec 1;317(6):E957-E972. (PMID: 31593505)
J Biol Chem. 2019 Jul 26;294(30):11369-11381. (PMID: 31175156)
Mol Biol Cell. 2001 Nov;12(11):3489-501. (PMID: 11694583)
Exp Mol Med. 2016 Jul 15;48(7):e245. (PMID: 27416781)
Mol Metab. 2017 Feb 01;6(4):315-316. (PMID: 28377870)
Circ Res. 1994 Nov;75(5):803-12. (PMID: 7923625)
Front Mol Biosci. 2020 Oct 20;7:583556. (PMID: 33195428)
Mol Biol Cell. 2013 Aug;24(16):2544-57. (PMID: 23804653)
Mol Cell Biol. 2004 Jul;24(14):6456-66. (PMID: 15226445)
Methods Enzymol. 2008;438:77-93. (PMID: 18413242)
Nat Rev Endocrinol. 2017 Mar;13(3):133-148. (PMID: 27739515)
Physiol Rev. 2013 Jul;93(3):993-1017. (PMID: 23899560)
Methods Mol Biol. 2008;457:347-66. (PMID: 19066040)
J Biol Chem. 2015 Sep 25;290(39):23528-42. (PMID: 26240143)
Cell Metab. 2005 Oct;2(4):263-72. (PMID: 16213228)
Diabetes. 2016 Jun;65(6):1577-89. (PMID: 27207531)
Traffic. 2004 Oct;5(10):763-71. (PMID: 15355512)
J Biol Chem. 2008 Oct 31;283(44):30311-21. (PMID: 18713752)
EMBO J. 2006 Dec 13;25(24):5648-58. (PMID: 17139247)
J Mol Endocrinol. 2020 Jan;64(1):R1-R19. (PMID: 31627187)
J Biol Chem. 2008 Sep 12;283(37):25115-25123. (PMID: 18617516)
EMBO J. 2004 May 19;23(10):2059-70. (PMID: 15116067)
Cell Metab. 2021 Apr 6;33(4):758-780. (PMID: 33826918)
Mol Biol Cell. 2008 Aug;19(8):3477-87. (PMID: 18550797)
Mol Biol Cell. 2004 Dec;15(12):5565-73. (PMID: 15469990)
Mol Biol Cell. 2004 Feb;15(2):870-82. (PMID: 14595108)
Mol Biol Cell. 2017 Jun 15;28(12):1667-1675. (PMID: 28450454)
Diabetes. 2007 Feb;56(2):414-23. (PMID: 17259386)
Nature. 2014 Aug 14;512(7513):190-3. (PMID: 25043022)
FASEB J. 2016 Mar;30(3):1037-50. (PMID: 26581601)
Mol Cell Proteomics. 2020 Oct;19(10):1706-1723. (PMID: 32680918)
Nat Protoc. 2016 Mar;11(3):456-75. (PMID: 26866790)
J Cell Biol. 1995 Feb;128(4):563-76. (PMID: 7532173)
Am J Physiol Cell Physiol. 2008 Oct;295(4):C1016-25. (PMID: 18701652)
J Cell Biol. 1995 May;129(4):999-1006. (PMID: 7744970)
J Biol Chem. 2007 Mar 23;282(12):9008-16. (PMID: 17220298)
J Physiol. 2014 Jan 15;592(2):351-75. (PMID: 24247980)
J Biol Chem. 2010 Jan 15;285(3):1653-60. (PMID: 19915010)
Cell Metab. 2021 Apr 6;33(4):748-757. (PMID: 33826917)
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9350-5. (PMID: 19470471)
Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19909-14. (PMID: 21041651)
Cell Metab. 2017 May 2;25(5):1147-1159.e10. (PMID: 28467931)
Mol Metab. 2021 Nov;53:101305. (PMID: 34303022)
Diabetes. 2017 Mar;66(3):598-612. (PMID: 27797909)
Biochem J. 2005 Oct 1;391(Pt 1):87-93. (PMID: 15971998)
Biochem Biophys Res Commun. 2001 Sep 21;287(2):445-54. (PMID: 11554749)
Cells. 2019 May 09;8(5):. (PMID: 31075957)
Nat Protoc. 2019 Mar;14(3):703-721. (PMID: 30804569)
Mol Biol Cell. 2004 Oct;15(10):4406-15. (PMID: 15254270)
Diabetologia. 2015 Jan;58(1):19-30. (PMID: 25280670)
Cell Metab. 2007 Apr;5(4):293-303. (PMID: 17403373)
J Biol Chem. 2000 Nov 17;275(46):36263-8. (PMID: 10967091)
Dev Cell. 2005 Jul;9(1):99-108. (PMID: 15992544)
J Biol Chem. 2006 Jan 6;281(1):484-90. (PMID: 16269413)
Cold Spring Harb Perspect Biol. 2011 Aug 01;3(8):a005264. (PMID: 21525512)
Nat Methods. 2015 Jan;12(1):51-4. (PMID: 25419960)
Nucleic Acids Res. 2019 Jan 8;47(D1):D419-D426. (PMID: 30407594)
Mol Biol Cell. 2021 Jan 1;32(1):57-73. (PMID: 33175605)
FASEB J. 2018 Apr;32(4):1741-1777. (PMID: 29242278)
Nature. 2003 Apr 10;422(6932):629-33. (PMID: 12687004)
Am J Physiol Endocrinol Metab. 2018 May 1;314(5):E478-E493. (PMID: 29089333)
Endocrinology. 2013 Oct;154(10):3502-14. (PMID: 23892475)
J Cell Biol. 2020 Jan 6;219(1):. (PMID: 31863584)
Curr Opin Cell Biol. 2010 Aug;22(4):506-12. (PMID: 20417083)
J Biol Chem. 2019 Dec 27;294(52):19988-19996. (PMID: 31740584)
J Clin Invest. 2001 Aug;108(3):371-81. (PMID: 11489930)
J Cell Biol. 2016 Jul 4;214(1):61-76. (PMID: 27354378)
FASEB J. 2006 Apr;20(6):705-7. (PMID: 16455755)
Endocrinology. 2009 Aug;150(8):3493-502. (PMID: 19406948)
J Biol Chem. 2001 Jun 22;276(25):22883-91. (PMID: 11297538)
Am J Physiol Endocrinol Metab. 2012 Nov 15;303(10):E1273-86. (PMID: 23011063)
BMJ Open Sport Exerc Med. 2017 Mar 1;2(1):e000143. (PMID: 28879026)

R01 DK125699 United States DK NIDDK NIH HHS; R01 DK125699 United States NH NIH HHS

Keywords: AMPK regulation of GLUT4; GLUT4 trafficking; GLUT4-proximal proteome; Human muscle cells

EC 2.7.11.31 (AMP-Activated Protein Kinases)
0 (Proteome)
0 (SLC2A4 protein, human)
0 (Glucose Transporter Type 4)

Date Created: 20231221 Date Completed: 20231227 Latest Revision: 20240210

20240210

PMC10753500

10.1242/jcs.261454

38126809