The MEF2A isoform is required for striated muscle-specific expression of the insulin-responsive GLUT4 glucose transporter

Silvia Mora, Jeffrey E. Pessin

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Previously, we have demonstrated that an MEF2 consensus sequence located between -473/-464 in the human GLUT4 gene was essential for both tissue- specific and hormonal/metabolic regulation of GLUT4 expression (Thai, M. V., Guruswamy, S., Cao, K. T., Pessin, J. E., and Olson, A. L. (1998) J. Biol. Chem. 273, 14285-14292). To identify the specific MEF2 isoform(s) responsible for GLUT4 expression, we studied the pattern of expression of the MEF2 isoforms in insulin-sensitive tissues. Both heart and skeletal muscle were found to express the MEF2A, MEF2C, and MEF2D isoforms but not MEF2B. However, only the MEF2A protein was selectively downregulated in insulin-deficient diabetes. Co-immunoprecipitation with isoform-specific antibodies revealed that, in the basal state, essentially all of the MEF2A protein was presented as a MEF2A-MEF2D heterodimer without any detectable MEF2A-MEF2A homodimers or MEF2A-MEF2C and MEF2C-MEF2D heterodimers. Electrophoretic mobility shift assays revealed that nuclear extracts from diabetic animals had reduced binding to the MEF2 binding site compared with extracts from control or insulin-treated animals. Furthermore, immunodepletion of the MEF2A-MEF2D complex from control extracts abolished binding to the MEF2 element. However, addition of MEF2A to diabetic nuclear extracts fully restored binding activity to the MEF2 element. These data strongly suggest that the MEF2A- MEF2D heterodimer is selectively decreased in insulin-deficient diabetes and is responsible for hormonally regulated expression of the GLUT4 gene.

Original languageEnglish (US)
Pages (from-to)16323-16328
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number21
DOIs
StatePublished - May 26 2000
Externally publishedYes

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Glucose Transporter Type 4
Striated Muscle
Facilitative Glucose Transport Proteins
Muscle
Protein Isoforms
MEF2 Transcription Factors
Insulin
Medical problems
Animals
Genes
Tissue
Electrophoretic mobility
Essential Genes
Consensus Sequence
Electrophoretic Mobility Shift Assay
Complex Mixtures
Immunoprecipitation
Assays
Myocardium
Skeletal Muscle

ASJC Scopus subject areas

  • Biochemistry

Cite this

The MEF2A isoform is required for striated muscle-specific expression of the insulin-responsive GLUT4 glucose transporter. / Mora, Silvia; Pessin, Jeffrey E.

In: Journal of Biological Chemistry, Vol. 275, No. 21, 26.05.2000, p. 16323-16328.

Research output: Contribution to journalArticle

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