NCS-1 inhibits insulin-stimulated GLUT4 translocation in 3T3L1 adipocytes through a phosphatidylinositol 4-kinase-dependent pathway

Silvia Mora, Paul L. Durham, Jeffery R. Smith, Andrew F. Russo, Andreas Jeromin, Jeffrey E. Pessin

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Expression of NCS-1 (neuronal calcium sensor-1, also termed frequenin) in 3T3L1 adipocytes strongly inhibited insulin-stimulated translocation of GLUT4 and insulin-responsive aminopeptidase. The effect of NCS-1 was specific for GLUT4 and the insulin-responsive aminopeptidase translocation as there was no effect on the trafficking of the cation-independent mannose 6-phosphate receptor or the GLUT1 glucose transporter isoform. Moreover, NCS-1 showed partial colocalization with GLUT4-EGFP in the perinuclear region. The inhibitory action of NCS-1 was independent of calcium sequestration since neither treatment with ionomycin nor endothelin-1, both of which elevated the intracellular calcium concentration, restored insulin-stimulated GLUT4 translocation. Furthermore, NCS-1 did not alter the insulin-stimulated protein kinase B (PKB/Akt) phosphorylation or the recruitment of Cbl to the plasma membrane. In contrast, expression of the NCS-1 effector phosphatidylinositol 4-kinase (PI 4-kinase) inhibited insulin-stimulated GLUT4 translocation, whereas co-transfection with an inactive PI 4-kinase mutant prevented the NCS-1-induced inhibition. These data demonstrate that PI 4-kinase functions to negatively regulate GLUT4 translocation through its interaction with NCS-1.

Original languageEnglish (US)
Pages (from-to)27494-27500
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number30
DOIs
StatePublished - Jul 26 2002
Externally publishedYes

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1-Phosphatidylinositol 4-Kinase
Adipocytes
Insulin
IGF Type 2 Receptor
Calcium
Proto-Oncogene Proteins c-akt
Phosphorylation
Ionomycin
Facilitative Glucose Transport Proteins
frequenin calcium sensor proteins
Endothelin-1
Cell membranes
Transfection
Cations
Protein Isoforms
Cell Membrane

ASJC Scopus subject areas

  • Biochemistry

Cite this

NCS-1 inhibits insulin-stimulated GLUT4 translocation in 3T3L1 adipocytes through a phosphatidylinositol 4-kinase-dependent pathway. / Mora, Silvia; Durham, Paul L.; Smith, Jeffery R.; Russo, Andrew F.; Jeromin, Andreas; Pessin, Jeffrey E.

In: Journal of Biological Chemistry, Vol. 277, No. 30, 26.07.2002, p. 27494-27500.

Research output: Contribution to journalArticle

Mora, Silvia ; Durham, Paul L. ; Smith, Jeffery R. ; Russo, Andrew F. ; Jeromin, Andreas ; Pessin, Jeffrey E. / NCS-1 inhibits insulin-stimulated GLUT4 translocation in 3T3L1 adipocytes through a phosphatidylinositol 4-kinase-dependent pathway. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 30. pp. 27494-27500.
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