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

doi:10.1074/jbc.M203669200

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

Journal article

Open access

Peer reviewed

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 and Jeffrey E Pessin

The Journal of biological chemistry, Vol.277(30), pp.27494-27500

07/26/2002

DOI: 10.1074/jbc.M203669200

PMID: 12011096

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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.

Phosphorylation

Cell Differentiation

Calcium - metabolism

Protein-Serine-Threonine Kinases

Neuronal Calcium-Sensor Proteins

1-Phosphatidylinositol 4-Kinase - metabolism

Muscle Proteins

Cell Nucleus - metabolism

Biological Transport

Cell Membrane - metabolism

Monosaccharide Transport Proteins - metabolism

Calcium-Binding Proteins - metabolism

Protein Structure, Tertiary

Proto-Oncogene Proteins - metabolism

Glucose Transporter Type 4

Neuropeptides - metabolism

Protein Transport

Proto-Oncogene Proteins c-akt

Animals

Adipocytes - metabolism

Protein Isoforms

Protein Binding

Mice

DNA, Complementary - metabolism

3T3 Cells

Microscopy, Fluorescence

Details

Title: Subtitle: NCS-1 inhibits insulin-stimulated GLUT4 translocation in 3T3L1 adipocytes through a phosphatidylinositol 4-kinase-dependent pathway
Creators: Silvia Mora - Department of Physiology and Biophysics, University of Iowa, 51 Newton Road, Iowa City, IA 52246, USA
Paul L Durham
Jeffery R Smith
Andrew F Russo
Andreas Jeromin
Jeffrey E Pessin
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.277(30), pp.27494-27500
DOI: 10.1074/jbc.M203669200
PMID: 12011096
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: DK 33823 / NIDDK NIH HHS DK 25295 / NIDDK NIH HHS HD 25969 / NICHD NIH HHS
Language: English
Date published: 07/26/2002
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center
Record Identifier: 9984020750902771

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