Usp25m protease regulates ubiquitin-like processing of TUG proteins to control GLUT4 glucose transporter translocation in adipocytes

The Journal of Biological Chemistry
Estifanos N HabtemichaelJonathan S Bogan

Abstract

Insulin stimulates the exocytic translocation of specialized vesicles in adipocytes, which inserts GLUT4 glucose transporters into the plasma membrane to enhance glucose uptake. Previous results support a model in which TUG (Tether containing a UBX domain for GLUT4) proteins trap these GLUT4 storage vesicles at the Golgi matrix and in which insulin triggers endoproteolytic cleavage of TUG to translocate GLUT4. Here, we identify the muscle splice form of Usp25 (Usp25m) as a protease required for insulin-stimulated TUG cleavage and GLUT4 translocation in adipocytes. Usp25m is expressed in adipocytes, binds TUG and GLUT4, dissociates from TUG-bound vesicles after insulin addition, and colocalizes with TUG and insulin-responsive cargoes in unstimulated cells. Previous results show that TUG proteolysis generates the ubiquitin-like protein, TUGUL (for TUGubiquitin-like). We now show that TUGUL modifies the kinesin motor protein, KIF5B, and that TUG proteolysis is required to load GLUT4 onto these motors. Insulin stimulates TUG proteolytic processing independently of phosphatidylinositol 3-kinase. In nonadipocytes, TUG cleavage can be reconstituted by transfection of Usp25m, but not the related Usp25a isoform, together with other prot...Continue Reading

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Citations

Jun 9, 2019·The Journal of Biological Chemistry·Amira KlipDavid E James
Jun 28, 2019·Frontiers in Cell and Developmental Biology·Andreas M ErnstJonathan S Bogan
Oct 22, 2020·Acta Biochimica Et Biophysica Sinica·Jin JuYong Zhang
Mar 10, 2021·Nature Metabolism·Estifanos N HabtemichaelJonathan S Bogan
Jul 6, 2020·Trends in Cell Biology·Gwyn W GouldNia J Bryant
May 22, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Gabriel WagnerMartin Bilban
Jul 13, 2021·Frontiers in Cell and Developmental Biology·Wenjing ZhuXiaoying Huang
Sep 1, 2021·Trends in Endocrinology and Metabolism : TEM·Skylar R Batty, Paul R Langlais

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