Munc18c Regulates Insulin-stimulated GLUT4 Translocation to the Transverse Tubules in Skeletal Muscle

Ahmir H. Khan, Debbie C. Thurmond, Chunmei Yang, Brian P. Ceresa, Curt D. Sigmund, Jeffrey E. Pessin

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

To examine the intracellular trafficking and translocation of GLUT4 in skeletal muscle, we have generated transgenic mouse lines that specifically express a GLUT4-EGFP (enhanced green fluorescent protein) fusion protein under the control of the human skeletal muscle actin promoter. These transgenic mice displayed EGFP fluorescence restricted to skeletal muscle and increased glucose tolerance characteristic of enhanced insulin sensitivity. The GLUT4-EGFP protein localized to the same intracellular compartment as the endogenous GLUT4 protein and underwent insulin- and exercise-stimulated translocation to both the sarcolemma and transverse-tubule membranes. Consistent with previous studies in adipocytes, overexpression of the syntaxin 4-binding Munc18c isoform, but not the related Munc18b isoform, in vivo specifically inhibited insulin-stimulated GLUT4-EGFP translocation. Surprisingly, however, Munc18c inhibited GLUT4 translocation to the transverse-tubule membrane without affecting translocation to the sarcolemma membrane. The ability of Munc18c to block GLUT4-EGFP translocation to the transverse-tubule membrane but not the sarcolemma membrane was consistent with substantially reduced levels of syntaxin 4 in the transverse-tubule membrane. Together, these data demonstrate that Munc18c specifically functions in the compartmentalized translocation of GLUT4 to the transverse-tubules in skeletal muscle. In addition, these results underscore the utility of this transgenic model to directly visualize GLUT4 translocation in skeletal muscle.

Original languageEnglish (US)
Pages (from-to)4063-4069
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number6
DOIs
StatePublished - Feb 9 2001
Externally publishedYes

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Muscle
Skeletal Muscle
Insulin
Membranes
Sarcolemma
Glucose Transporter Type 4
Qa-SNARE Proteins
Transgenic Mice
Protein Isoforms
Adipocytes
Insulin Resistance
Actins
Fusion reactions
Fluorescence
Glucose
Proteins
enhanced green fluorescent protein

ASJC Scopus subject areas

  • Biochemistry

Cite this

Khan, A. H., Thurmond, D. C., Yang, C., Ceresa, B. P., Sigmund, C. D., & Pessin, J. E. (2001). Munc18c Regulates Insulin-stimulated GLUT4 Translocation to the Transverse Tubules in Skeletal Muscle. Journal of Biological Chemistry, 276(6), 4063-4069. https://doi.org/10.1074/jbc.M007419200

Munc18c Regulates Insulin-stimulated GLUT4 Translocation to the Transverse Tubules in Skeletal Muscle. / Khan, Ahmir H.; Thurmond, Debbie C.; Yang, Chunmei; Ceresa, Brian P.; Sigmund, Curt D.; Pessin, Jeffrey E.

In: Journal of Biological Chemistry, Vol. 276, No. 6, 09.02.2001, p. 4063-4069.

Research output: Contribution to journalArticle

Khan, AH, Thurmond, DC, Yang, C, Ceresa, BP, Sigmund, CD & Pessin, JE 2001, 'Munc18c Regulates Insulin-stimulated GLUT4 Translocation to the Transverse Tubules in Skeletal Muscle', Journal of Biological Chemistry, vol. 276, no. 6, pp. 4063-4069. https://doi.org/10.1074/jbc.M007419200
Khan, Ahmir H. ; Thurmond, Debbie C. ; Yang, Chunmei ; Ceresa, Brian P. ; Sigmund, Curt D. ; Pessin, Jeffrey E. / Munc18c Regulates Insulin-stimulated GLUT4 Translocation to the Transverse Tubules in Skeletal Muscle. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 6. pp. 4063-4069.
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