| First Author | Cheviet S | Year | 2006 |
| Journal | J Cell Sci | Volume | 119 |
| Issue | Pt 14 | Pages | 2912-20 |
| PubMed ID | 16787939 | Mgi Jnum | J:111732 |
| Mgi Id | MGI:3654783 | Doi | 10.1242/jcs.03037 |
| Citation | Cheviet S, et al. (2006) Tomosyn-1 is involved in a post-docking event required for pancreatic beta-cell exocytosis. J Cell Sci 119(Pt 14):2912-20 |
| abstractText | 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 beta-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 beta-cells tomosyn-1 was found to be concentrated in cellular compartments enriched in insulin-containing secretory granules. Silencing of tomosyn-1 in the rat beta-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 beta-cells in response to insulin secretagogues. |
