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 language | English |
|---|---|
| Pages (from-to) | 574-581 |
| Number of pages | 8 |
| Journal | Diabetes |
| Volume | 55 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2006 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
Tomosyn is expressed in β-cells and negatively regulates insulin exocytosis. / Zhang, Wei; Lilja, Lena; Mandic, Slavena A.; Gromada, Jesper; Smidt, Kamille; Janson, Juliette; Takai, Yoshimi; Bark, Christina; Berggren, Per Olof; Meister, Björn.
In: Diabetes, Vol. 55, No. 3, 01.03.2006, p. 574-581.Research output: Contribution to journal › Article
}
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 - 2006/3/1
Y1 - 2006/3/1
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.
UR - http://www.scopus.com/inward/record.url?scp=33644783907&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644783907&partnerID=8YFLogxK
U2 - 10.1002/sia.2299
DO - 10.1002/sia.2299
M3 - Article
C2 - 16505218
AN - SCOPUS:33644783907
VL - 55
SP - 574
EP - 581
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 3
ER -