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

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.

Bezzi, Paola (author)
Ivarsson, RositaLund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups(Swepub:lu)mphy-riv (author)
Renström, ErikLund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups(Swepub:lu)mphy-ere (author)
Viertl, David (author)
Kasas, Sandor (author)
Catsicas, Stefan (author)
Regazzi, Romano (author)
Diabetes - öpatofysiologiForskargrupper vid Lunds universitet (creator_code:org_t)

In:Journal of Cell Science: The Company of Biologists119:14, s. 2912-29200021-95331477-9137

By the author/editor: Cheviet, Severin ...; Bezzi, Paola; Ivarsson, Rosita; Renström, Erik; Viertl, David; Kasas, Sandor; show more...; Catsicas, Stefan; Regazzi, Romano; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.