DHHC7 palmitoylates glucose transporter 4 (Glut4) and regulates Glut4 membrane translocation

Keyong Du, Shoko Murakami, Yingmin Sun, Casey L. Kilpatrick, Bernhard Luscher

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Insulin-dependent translocation of glucose transporter 4 (Glut4) to the plasma membrane plays a key role in the dynamic regulation of glucose homeostasis.Werecently 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 andDHHC7KOin 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.

Original languageEnglish (US)
Pages (from-to)2979-2991
Number of pages13
JournalJournal of Biological Chemistry
Volume292
Issue number7
DOIs
StatePublished - Feb 17 2017

Fingerprint

Facilitative Glucose Transport Proteins
Lipoylation
Membranes
Acyltransferases
Adipocytes
Insulin
Glucose
Homeostasis
Glucose Intolerance
Cell membranes
Hyperglycemia
Muscle
Adipose Tissue
Cell Membrane
Tissue
Muscles

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "DHHC7 palmitoylates glucose transporter 4 (Glut4) and regulates Glut4 membrane translocation",
abstract = "Insulin-dependent translocation of glucose transporter 4 (Glut4) to the plasma membrane plays a key role in the dynamic regulation of glucose homeostasis.Werecently 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 andDHHC7KOin 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.",
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DHHC7 palmitoylates glucose transporter 4 (Glut4) and regulates Glut4 membrane translocation. / Du, Keyong; Murakami, Shoko; Sun, Yingmin; Kilpatrick, Casey L.; Luscher, Bernhard.

In: Journal of Biological Chemistry, Vol. 292, No. 7, 17.02.2017, p. 2979-2991.

Research output: Contribution to journalArticle

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