Tomosyn is expressed in β-cells and negatively regulates insulin exocytosis

Wei Zhang, Lena Lilja, Slavena A. Mandic, Jesper Gromada, Kamille Smidt, Juliette Janson, Yoshimi Takai, Christina Bark, Per Olof Berggren, Björn Meister

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Tomosyn, a syntaxin-binding protein, is capable of dissociating mammalian homolog of the Caenorhabditis elegans unc-18 gene from syntaxin and is involved in the regulation of exocytosis. We have investigated the expression, cellular localization, and functional role of tomosyn in pancreatic β-cells. Western blotting revealed a 130-kDa protein corresponding to tomosyn in insulin-secreting β-cell lines. RT-PCR amplification showed that b-, m-, and s-tomosyn isoform mRNAs are expressed in β-cell lines and rat pancreatic islets. Immunohistochemistry revealed punctate tomosyn immunoreactivity in the cytoplasm of insulin-, glucagon-, pancreatic polypeptide-, and somatostatin-containing islet cells. Syntaxin 1 coimmunoprecipitated with tomosyn in extracts of insulin-secreting cells. Overexpression of m-tomosyn in mouse β-cells significantly decreased exocytosis, whereas inhibition of tomosyn expression by small interfering RNA increased exocytosis. Hence, in the pancreatic β-cell, tomosyn negatively regulates insulin exocytosis.

Original languageEnglish (US)
Pages (from-to)574-581
Number of pages8
JournalDiabetes
Volume55
Issue number3
DOIs
StatePublished - Mar 2006

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Zhang, W., Lilja, L., Mandic, S. A., Gromada, J., Smidt, K., Janson, J., Takai, Y., Bark, C., Berggren, P. O., & Meister, B. (2006). Tomosyn is expressed in β-cells and negatively regulates insulin exocytosis. Diabetes, 55(3), 574-581. https://doi.org/10.2337/diabetes.55.03.06.db05-0015