title: Adenovirus-mediated silencing of synaptotagmin 9 inhibits Ca2+-dependent insulin secretion in islets.
abstract: Synaptotagmins (Syts) are involved in Ca(2+)-dependent insulin release. However, which Syt isoform is functional in primary beta-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 Ca(2+) sensor for beta-cell secretion.
authors.affiliation: Department of Cell Physiology and Metabolism, University Medical Center, 1211 Geneva 4, Switzerland.
authors.forename: Mariella
authors.initials: M
authors.lastname: Iezzi
authors.forename: Lena
authors.initials: L
authors.lastname: Eliasson
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Fukuda
authors.forename: Claes B
authors.initials: CB
authors.lastname: Wollheim
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism* / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D050857:Synaptotagmins
chemical_list: D002135:Calcium-Binding Proteins; D007328:Insulin; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C483193:Syt9 protein, rat; D050857:Synaptotagmins; D002118:Calcium