title: Tctex1d2 Is a Negative Regulator of GLUT4 Translocation and Glucose Uptake.
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-dependent manner and inhibit 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.
authors.affiliation: Department of Medicine and Molecular Science (Y.S., S.O., E.Y., M.Y.), Gunma University Graduate School of Medicine, Gunma 371-8511, Japan; and Departments of Medicine and Molecular Pharmacology (J.E.P.), Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shimoda
authors.affiliation: Department of Medicine and Molecular Science (Y.S., S.O., E.Y., M.Y.), Gunma University Graduate School of Medicine, Gunma 371-8511, Japan; and Departments of Medicine and Molecular Pharmacology (J.E.P.), Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Okada
authors.affiliation: Department of Medicine and Molecular Science (Y.S., S.O., E.Y., M.Y.), Gunma University Graduate School of Medicine, Gunma 371-8511, Japan; and Departments of Medicine and Molecular Pharmacology (J.E.P.), Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: Eijiro
authors.initials: E
authors.lastname: Yamada
authors.affiliation: Department of Medicine and Molecular Science (Y.S., S.O., E.Y., M.Y.), Gunma University Graduate School of Medicine, Gunma 371-8511, Japan; and Departments of Medicine and Molecular Pharmacology (J.E.P.), Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Pessin
authors.affiliation: Department of Medicine and Molecular Science (Y.S., S.O., E.Y., M.Y.), Gunma University Graduate School of Medicine, Gunma 371-8511, Japan; and Departments of Medicine and Molecular Pharmacology (J.E.P.), Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D003598:Cytoskeletal Proteins; D003847:Deoxyglucose / Q000737:chemistry; D004398:Dyneins / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D050765:Qa-SNARE Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C533386:Dynlt1b protein, mouse; D051275:Glucose Transporter Type 4; D050765:Qa-SNARE Proteins; D011993:Recombinant Fusion Proteins; C495693:Slc2a4 protein, mouse; C000603510:Tctex1d2 protein, mouse; D049452:Green Fluorescent Proteins; D003847:Deoxyglucose; D004398:Dyneins; D005947:Glucose