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First published online 20 June 2006
doi: 10.1242/jcs.03037

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Tomosyn-1 is involved in a post-docking event required for pancreatic ß-cell exocytosis

¹ Department of Cell Biology and Morphology, Rue du Bugnon 9, University of Lausanne, 1005 Lausanne, Switzerland
² Department of Clinical Sciences, Malmö, Lund University, Sweden
³ Laboratoire de Neurobiologie Cellulaire, Ecole Polytechnique Fédérale, Lausanne, Switzerland

^* Author for correspondence (e-mail: Romano.Regazzi{at}unil.ch)

Accepted 5 May 2006

Although the assembly of a ternary complex between the SNARE proteins syntaxin-1, SNAP25 and VAMP2 is known to be crucial for insulin exocytosis, the mechanisms controlling this key event are poorly understood. We found that pancreatic ß-cells express different isoforms of tomosyn-1, a syntaxin-1-binding protein possessing a SNARE-like motif. Using atomic force microscopy we show that the SNARE-like domain of tomosyn-1 can form a complex with syntaxin-1 and SNAP25 but displays binding forces that are weaker than those observed for VAMP2 (237±13 versus 279±3 pN). In pancreatic ß-cells tomosyn-1 was found to be concentrated in cellular compartments enriched in insulin-containing secretory granules. Silencing of tomosyn-1 in the rat ß-cell line INS-1E by RNA interference did not affect the number of secretory granules docked at the plasma membrane but led to a reduction in stimulus-induced exocytosis. Replacement of endogenous tomosyn-1 with mouse tomosyn-1, which differs in the nucleotide sequence from its rat homologue and escapes silencing, restored a normal secretory rate. Taken together, our data suggest that tomosyn-1 is involved in a post-docking event that prepares secretory granules for fusion and is necessary to sustain exocytosis of pancreatic ß-cells in response to insulin secretagogues.

Key words: Insulin, Exocytosis, SNARE, TIRF

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