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Tomosyn is expressed in beta-cells and negatively regulates insulin exocytosis
- Zhang, W (author)
- Lilja, L (author)
- Mandic, SA (author)
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- Gromada, J (author)
- Smidt, K (author)
- Janson, J (author)
- Takai, Y (author)
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- (creator_code:org_t)
- American Diabetes Association, 2006
- 2006
- English.
- In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:3, s. 574-581
- Journal article (peer-reviewed)
Abstract
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- 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.
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- Zhang, W
- Lilja, L
- Mandic, SA
- Gromada, J
- Smidt, K
- Janson, J
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- Takai, Y
- Bark, C
- Berggren, PO
- Meister, B
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- Diabetes
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- Karolinska Institutet
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