Syntaxin 4 Expression Affects Glucose Transporter 8 Translocation and Embryo Survival

Amanda Hoehn Wyman, Maggie Chi, Joan Riley, Mary O. Carayannopoulos, Chunmei Yang, Kenneth J. Coker, Jeffrey E. Pessin, Kelle H. Moley

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Target-soluble N-ethylmaleimide-sensitive factor attachment protein receptors (t-SNAREs) are receptors that facilitate vesicle and target membrane fusion. Syntaxin 4 is the t-SNARE critical for insulin-stimulated glucose transporter 4 (GLUT4)-plasma membrane fusion in adipocytes. GLUT8 is a novel IGF-I/insulin-regulated glucose transporter expressed in the mouse blastocyst. Similar to GLUT4, GLUT8 translocates to the plasma membrane to increase glucose uptake at a stage in development when glucose serves as the main substrate. Any decrease in GLUT8 cell surface expression results in increased apoptosis and pregnancy loss. Previous studies have also shown that disruption of the syntaxin 4 (Stx4a) gene results in early embryonic lethality before embryonic d 7.5. We have now demonstrated that syntaxin 4 protein is localized predominantly to the apical plasma membrane of the murine blastocyst. Stx4a inheritance, as detected by protein expression, occurs with the expected Mendelian frequency up to embryonic d 4.5. In parallel, 22% of the blastocysts from Stx4a+/- matings had no significant insulin-stimulated translocation of GLUT8 whereas 77% displayed either partial or complete translocation to the apical plasma membrane. This difference in GLUT8 translocation directly correlated with one-third of blastocysts from Stx4a+/- mating having reduced rates of insulin-stimulated glucose uptake and 67% with wild-type rates. These data demonstrate that the lack of syntaxin 4 expression results in abnormal movement of GLUT8 in response to insulin, decreased insulin-stimulated glucose uptake, and increased apoptosis. Thus, syntaxin 4 functions as the necessary t-SNARE protein responsible for correct fusion of the GLUT8-containing vesicle with the plasma membrane in the mouse blastocyst.

Original languageEnglish (US)
Pages (from-to)2096-2102
Number of pages7
JournalMolecular Endocrinology
Volume17
Issue number10
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

Fingerprint

Qa-SNARE Proteins
Facilitative Glucose Transport Proteins
Blastocyst
Embryonic Structures
Cell Membrane
Insulin
N-Ethylmaleimide-Sensitive Proteins
Glucose
Membrane Fusion
Proteins
Apoptosis
SNARE Proteins
Insulin Receptor
Dyskinesias
Insulin-Like Growth Factor I
Adipocytes
Pregnancy
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Wyman, A. H., Chi, M., Riley, J., Carayannopoulos, M. O., Yang, C., Coker, K. J., ... Moley, K. H. (2003). Syntaxin 4 Expression Affects Glucose Transporter 8 Translocation and Embryo Survival. Molecular Endocrinology, 17(10), 2096-2102. https://doi.org/10.1210/me.2002-0240

Syntaxin 4 Expression Affects Glucose Transporter 8 Translocation and Embryo Survival. / Wyman, Amanda Hoehn; Chi, Maggie; Riley, Joan; Carayannopoulos, Mary O.; Yang, Chunmei; Coker, Kenneth J.; Pessin, Jeffrey E.; Moley, Kelle H.

In: Molecular Endocrinology, Vol. 17, No. 10, 01.10.2003, p. 2096-2102.

Research output: Contribution to journalArticle

Wyman, AH, Chi, M, Riley, J, Carayannopoulos, MO, Yang, C, Coker, KJ, Pessin, JE & Moley, KH 2003, 'Syntaxin 4 Expression Affects Glucose Transporter 8 Translocation and Embryo Survival', Molecular Endocrinology, vol. 17, no. 10, pp. 2096-2102. https://doi.org/10.1210/me.2002-0240
Wyman AH, Chi M, Riley J, Carayannopoulos MO, Yang C, Coker KJ et al. Syntaxin 4 Expression Affects Glucose Transporter 8 Translocation and Embryo Survival. Molecular Endocrinology. 2003 Oct 1;17(10):2096-2102. https://doi.org/10.1210/me.2002-0240
Wyman, Amanda Hoehn ; Chi, Maggie ; Riley, Joan ; Carayannopoulos, Mary O. ; Yang, Chunmei ; Coker, Kenneth J. ; Pessin, Jeffrey E. ; Moley, Kelle H. / Syntaxin 4 Expression Affects Glucose Transporter 8 Translocation and Embryo Survival. In: Molecular Endocrinology. 2003 ; Vol. 17, No. 10. pp. 2096-2102.
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