DHHC7 Palmitoylates Glucose Transporter 4 (Glut4) and Regulates Glut4 Membrane Translocation
| Autor: | Casey L. Kilpatrick, Keyong Du, Bernhard Lüscher, Shoko Murakami, Yingmin Sun |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system diseases Palmitic Acid Adipose tissue Biology Biochemistry Mice 03 medical and health sciences Protein acylation 0302 clinical medicine Palmitoylation 3T3-L1 Cells Membrane Biology Adipocytes Animals Humans Insulin Glucose homeostasis Palmitoyl acyltransferase Molecular Biology Mice Knockout Glucose Transporter Type 4 Cell Membrane Glucose transporter nutritional and metabolic diseases Cell Biology Glucose Tolerance Test musculoskeletal system Mice Inbred C57BL Protein Transport HEK293 Cells 030104 developmental biology Hyperglycemia biology.protein Ectopic expression Acyltransferases hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery GLUT4 |
| Zdroj: | Journal of Biological Chemistry. 292:2979-2991 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m116.747139 |
| Popis: | Insulin-dependent translocation of glucose transporter 4 (Glut4) to the plasma membrane plays a key role in the dynamic regulation of glucose homeostasis. We recently showed that this process is critically dependent on palmitoylation of Glut4 at Cys-223. To gain further insights into the regulation of Glut4 palmitoylation, we set out to identify the palmitoyl acyltransferase (PAT) involved. Here we report that among 23 mammalian DHHC proteins, DHHC7 is the major Glut4 PAT, based on evidence that ectopic expression of DHHC7 increased Glut4 palmitoylation, whereas DHHC7 knockdown in 3T3-L1 adipocytes and DHHC7 KO in adipose tissue and muscle decreased Glut4 palmitoylation. Moreover, inactivation of DHHC7 suppressed insulin-dependent Glut4 membrane translocation in both 3T3-L1 adipocytes and primary adipocytes. Finally, DHHC7 KO mice developed hyperglycemia and glucose intolerance, thereby confirming that DHHC7 represents the principal PAT for Glut4 and that this mechanism is essential for insulin-regulated glucose homeostasis. |
| Databáze: | OpenAIRE |
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