Regulation of insulin-responsive aminopeptidase expression and targeting in the insulin-responsive vesicle compartment of glucose transporter isoform 4-deficient cardiomyocytes

Molecular Endocrinology
E Dale AbelKonstantin V Kandror

Abstract

In adipocytes and cardiac or skeletal muscle, glucose transporter isoform 4 (GLUT4) is targeted to insulin-responsive intracellular membrane vesicles (IRVs) that contain several membrane proteins, including insulin-responsive aminopeptidase (IRAP) that completely colocalizes with GLUT4 in basal and insulin-treated cells. Cardiac GLUT4 content is reduced by 65-85% in IRAP knockout mice, suggesting that IRAP may regulate the targeting or degradation of GLUT4. To determine whether GLUT4 is required for maintenance of IRAP content within IRVs, we studied the expression and cellular localization of IRAP and other GLUT4 vesicle-associated proteins, in hearts of mice with cardiac-specific deletion of GLUT4 (G4H-/-). In G4H-/- hearts, IRAP content was reduced by 60%, but the expression of other vesicle-associated proteins, namely cellugyrin, IGF-II/mannose-6-phosphate, and transferrin receptors, secretory carrier-associated membrane proteins and vesicle-associated membrane protein were unchanged. Using sucrose gradient centrifugation and cell surface biotinylation, we found that IRAP content in 50-80S vesicles where GLUT4 vesicles normally sediment was markedly depleted in G4H-/- hearts, and the remaining IRAP was found in the heavy me...Continue Reading

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Citations

Aug 21, 2008·The Journal of Biological Chemistry·Jun ShiKonstantin V Kandror
Aug 24, 2013·Molecular Biology of the Cell·Guanrong HuangKonstantin V Kandror
Jan 17, 2009·Cardiovascular Research·Jordan J WrightE Dale Abel
Nov 13, 2010·Veterinary Clinical Pathology·Teckla L WebbChristine S Olver
May 6, 2016·Frontiers in Physiology·Francisco WestermeierSergio Lavandero
Jun 7, 2011·Journal of Molecular and Cellular Cardiology·Kayla M PoundE Douglas Lewandowski
Oct 28, 2016·European Journal of Clinical Investigation·Maria MizamtsidiAndromachi Vryonidou
Oct 25, 2006·The Biochemical Journal·Tsung-Yin J YehNai-Wen Chi
Feb 11, 2011·Traffic·Konstantin V Kandror, Paul F Pilch
Jun 19, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Bao-Wei WangKou-Gi Shyu
Dec 14, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·Ping ZhaoXinzhou Yang

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