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    Diabetes. 2006 Mar;55(3):574-81.

    Tomosyn is expressed in beta-cells and negatively regulates insulin exocytosis.

    Zhang W, Lilja L, Mandic SA, Gromada J, Smidt K, Janson J, Takai Y, Bark C, Berggren PO, Meister B.

    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

    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 beta-cells. Western blotting revealed a 130-kDa protein corresponding to tomosyn in insulin-secreting beta-cell lines. RT-PCR amplification showed that b-, m-, and s-tomosyn isoform mRNAs are expressed in beta-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 beta-cells significantly decreased exocytosis, whereas inhibition of tomosyn expression by small interfering RNA increased exocytosis. Hence, in the pancreatic beta-cell, tomosyn negatively regulates insulin exocytosis.

    PMID: 16505218 [PubMed - indexed for MEDLINE]

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