TY - JOUR
T1 - Tomosyn is expressed in β-cells and negatively regulates insulin exocytosis
AU - Zhang, Wei
AU - Lilja, Lena
AU - Mandic, Slavena A.
AU - Gromada, Jesper
AU - Smidt, Kamille
AU - Janson, Juliette
AU - Takai, Yoshimi
AU - Bark, Christina
AU - Berggren, Per Olof
AU - Meister, Björn
PY - 2006/3
Y1 - 2006/3
N2 - 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.
AB - 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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U2 - 10.2337/diabetes.55.03.06.db05-0015
DO - 10.2337/diabetes.55.03.06.db05-0015
M3 - Article
C2 - 16505218
AN - SCOPUS:33644783907
VL - 55
SP - 574
EP - 581
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 3
ER -