Tctex1d2 is a negative regulator of GLUT4 translocation and glucose uptake

Yoko Shimoda, Shuichi Okada, Eijiro Yamada, Jeffrey E. Pessin, Masanobu Yamada

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Tctex1d2 (Tctex1 domain containing 2) is an open reading frame that encodes for a functionally unknown protein that contains a Tctex1 domain found in dynein light chain family members. Examination of gene expression during adipogenesis demonstrated a marked increase in Tctex1d2 protein expression that was essentially undetectable in preadipocytes and markedly induced during 3T3-L1 adipocyte differentiation. Tctex1d2 overexpression significantly inhibited insulin-stimulated glucose transporter 4 (GLUT4) translocation and 2-deoxyglucose uptake. In contrast, Tctex1d2 knockdown significantly increased insulin-stimulated GLUT4 translocation and 2-deoxyglucose uptake. However, acute insulin stimulation (up to 30 min) in 3T3-L1 adipocytes with overexpression or knockdown of Tctex1d2 had no effect on Akt phosphorylation, a critical signal transduction target required for GLUT4 translocation. Although overexpression of Tctex1d2 had no significant effect on GLUT4 internalization, Tctex1d2 was found to associate with syntaxin 4 in an insulin-dependentmannerandinhibit Doc2b binding to syntaxin 4. In addition, glucose-dependent insulinotropic polypeptide rescued the Tctex1d2 inhibition of insulin-stimulated GLUT4 translocation by suppressing the Tctex1d2-syntaxin 4 interaction and increasing Doc2b-Synatxin4 interactions. Taking these results together, we hypothesized that Tctex1d2 is a novel syntaxin 4 binding protein that functions as a negative regulator of GLUT4 plasma membrane translocation through inhibition of the Doc2b-syntaxin 4 interaction.

Original languageEnglish (US)
Pages (from-to)3548-3558
Number of pages11
JournalEndocrinology
Volume156
Issue number10
DOIs
StatePublished - Oct 1 2015

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Facilitative Glucose Transport Proteins
Qa-SNARE Proteins
Glucose
Insulin
Deoxyglucose
Adipocytes
Dyneins
Adipogenesis
Open Reading Frames
Signal Transduction
Carrier Proteins
Proteins
Phosphorylation
Cell Membrane
Gene Expression
Peptides

ASJC Scopus subject areas

  • Endocrinology

Cite this

Tctex1d2 is a negative regulator of GLUT4 translocation and glucose uptake. / Shimoda, Yoko; Okada, Shuichi; Yamada, Eijiro; Pessin, Jeffrey E.; Yamada, Masanobu.

In: Endocrinology, Vol. 156, No. 10, 01.10.2015, p. 3548-3558.

Research output: Contribution to journalArticle

Shimoda, Yoko ; Okada, Shuichi ; Yamada, Eijiro ; Pessin, Jeffrey E. ; Yamada, Masanobu. / Tctex1d2 is a negative regulator of GLUT4 translocation and glucose uptake. In: Endocrinology. 2015 ; Vol. 156, No. 10. pp. 3548-3558.
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