Tomosyn is a novel Akt substrate mediating insulin-dependent GLUT4 exocytosis

Koki Nagano, Hiroshi Takeuchi, Jing Gao, Yoshihide Mori, Takahito Otani, Daguang Wang, Masato Hirata

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Insulin triggers glucose uptake into skeletal muscle and adipose tissues by gaining the available number of glucose transporter 4 (GLUT4) on the cell surface. GLUT4-loaded vesicles are targeted to plasma membrane from the intracellular reservoir through multiple trafficking and fusion processes that are mainly regulated by Akt. However, it is still largely unknown how GLUT4 expression in the cell surface is promoted by insulin. In the present study, we identified tomosyn at Ser-783 as a possible Akt-substrate motif and examined whether the phosphorylation at Ser-783 is involved in the regulation of GLUT4 expression. Both Akt1 and Akt2 phosphorylated the wild-type tomosyn, but not the mutant tomosyn in which Ser-783 was replaced with Ala. Phosphorylation of tomosyn at Ser-783 was also observed in the intact cells by insulin stimulation, which was blocked by PI3K inhibitor, LY294002. In vitro pull-down assay showed that phosphorylation of tomosyn at Ser-783 by Akt inhibited the interaction with syntaxin 4. Insulin stimulation increased GLUT4 in the cell surface of CHO-K1 cells to promote glucose uptake, however exogenous expression of the mutant tomosyn attenuated the increase by insulin. These results suggest that Ser-783 of tomosyn is a target of Akt and is implicated in the interaction with syntaxin 4.

Original languageEnglish
Pages (from-to)62-71
Number of pages10
JournalInternational Journal of Biochemistry and Cell Biology
Volume62
DOIs
Publication statusPublished - May 1 2015

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Facilitative Glucose Transport Proteins
Exocytosis
Phosphorylation
Insulin
Qa-SNARE Proteins
Substrates
Glucose
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
CHO Cells
Cell membranes
Phosphatidylinositol 3-Kinases
Muscle
Adipose Tissue
Assays
Skeletal Muscle
Fusion reactions
Cell Membrane
Tissue
Muscles

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

Cite this

Tomosyn is a novel Akt substrate mediating insulin-dependent GLUT4 exocytosis. / Nagano, Koki; Takeuchi, Hiroshi; Gao, Jing; Mori, Yoshihide; Otani, Takahito; Wang, Daguang; Hirata, Masato.

In: International Journal of Biochemistry and Cell Biology, Vol. 62, 01.05.2015, p. 62-71.

Research output: Contribution to journalArticle

Nagano, Koki ; Takeuchi, Hiroshi ; Gao, Jing ; Mori, Yoshihide ; Otani, Takahito ; Wang, Daguang ; Hirata, Masato. / Tomosyn is a novel Akt substrate mediating insulin-dependent GLUT4 exocytosis. In: International Journal of Biochemistry and Cell Biology. 2015 ; Vol. 62. pp. 62-71.
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