HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, W. Articles by Meister, B. Search for Related Content PubMed PubMed Citation Articles by Zhang, W. Articles by Meister, B. Social Bookmarking                What's this?

Tomosyn Is Expressed in ß-Cells and Negatively Regulates Insulin Exocytosis

¹ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
² The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
³ Department of Pharmacology, University of Aarhus, Aarhus, Denmark
⁴ Lilly Research Laboratories, Hamburg, Germany
⁵ Department of Molecular Biology and Biochemistry, Osaka University Medical School, Suita, Japan

Address correspondence and reprint requests to Prof. Per-Olof Berggren, The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska University Hospital, L3, Karolinska Institutet, SE-171 76 Stockholm, Sweden. E-mail: per-olof.berggren{at}ki.se

Abbreviations: GFP, green fluorescent protein; hGH, human growth hormone; Munc-18, mammalian homolog of the Caenorhabditis elegans unc-18 gene; siRNA, small interfering RNA; SNAP-25, synaptosomal-associated protein of 25 kDa; SNARE, soluble N-ethylmaleimide–sensitive factor attachment protein receptor

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

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. O. Gracheva, A. O. Burdina, D. Touroutine, M. Berthelot-Grosjean, H. Parekh, and J. E. Richmond Tomosyn negatively regulates both synaptic transmitter and neuropeptide release at the C. elegans neuromuscular junction J. Physiol., December 15, 2007; 585(3): 705 - 709. [Abstract] [Full Text] [PDF]

				Y. M. Leung, E. P. Kwan, B. Ng, Y. Kang, and H. Y. Gaisano SNAREing Voltage-Gated K+ and ATP-Sensitive K+ Channels: Tuning {beta}-Cell Excitability with Syntaxin-1A and Other Exocytotic Proteins Endocr. Rev., October 1, 2007; 28(6): 653 - 663. [Abstract] [Full Text] [PDF]

				E. P. Kwan, L. Xie, L. Sheu, T. Ohtsuka, and H. Y. Gaisano Interaction Between Munc13-1 and RIM Is Critical for Glucagon-Like Peptide-1 Mediated Rescue of Exocytotic Defects in Munc13-1 Deficient Pancreatic {beta}-Cells Diabetes, October 1, 2007; 56(10): 2579 - 2588. [Abstract] [Full Text] [PDF]

				E. O. Gracheva, A. O. Burdina, D. Touroutine, M. Berthelot-Grosjean, H. Parekh, and J. E. Richmond Tomosyn Negatively Regulates CAPS-Dependent Peptide Release at Caenorhabditis elegans Synapses J. Neurosci., September 19, 2007; 27(38): 10176 - 10184. [Abstract] [Full Text] [PDF]

				S. E. Gladycheva, A. D. Lam, J. Liu, M. D'Andrea-Merrins, O. Yizhar, S. I. Lentz, U. Ashery, S. A. Ernst, and E. L. Stuenkel Receptor-mediated Regulation of Tomosyn-Syntaxin 1A Interactions in Bovine Adrenal Chromaffin Cells J. Biol. Chem., August 3, 2007; 282(31): 22887 - 22899. [Abstract] [Full Text] [PDF]