Adenovirus-mediated silencing of Synaptotagmin 9 inhibits Ca ²⁺-dependent insulin secretion in islets

Synaptotagmins (Syts) are involved in Ca²⁺-dependent insulin release. However, which Syt isoform is functional in primary β-cells remains unknown. We demonstrate by electron microscopy of pancreatic islets, the association of Syt 9 with insulin granules. Silencing of Syt 9 by RNA interference adenovirus in islet cells had no effect on the expression of Syt 5, Syt 7 and Syt 3 isoforms. The latter was localized at the plasma membrane of pancreatic polypeptide cells. Insulin release in response to glucose or tolbutamide was strongly inhibited in Syt 9 deficient islets, whereas exocytosis potentiated by raising cAMP levels, was unaltered. Thus, Syt 9 may act as Ca²⁺ sensor for β-cell secretion.