Adenovirus-mediated silencing of Synaptotagmin 9 inhibits Ca2+-dependent insulin secretion in islets

被引:45
作者
Iezzi, M
Eliasson, L
Fukuda, M
Wollheim, CB [1 ]
机构
[1] Univ Geneva, Med Ctr, Dept Cell Physiol & Metab, CH-1211 Geneva, Switzerland
[2] Dept Expt Med Sci, Div Diabet Metab & Endocrinol, S-22184 Lund, Sweden
[3] RIKEN, Fukuda Initiat Res Unit, Wako, Saitama 3510198, Japan
来源
FEBS LETTERS | 2005年 / 579卷 / 23期
关键词
pancreatic islets; insulin exocytosis; electron; microscopy; RNA interference; beta-cell;
D O I
10.1016/j.febslet.2005.08.047
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Synaptotagmins (Syts) are involved in Ca2+-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 Ca2+ sensor for beta-cell secretion. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:5241 / 5246
页数:6
相关论文
共 29 条
[1]   Fast exocytosis with few Ca2+ channels in insulin-secreting mouse pancreatic B cells [J].
Barg, S ;
Ma, XS ;
Eliasson, L ;
Galvanovskis, J ;
Göpel, SO ;
Obermüller, S ;
Platzer, J ;
Renström, E ;
Trus, M ;
Atlas, D ;
Striessnig, J ;
Rorsman, P .
BIOPHYSICAL JOURNAL, 2001, 81 (06) :3308-3323
[2]   Synaptotagmin III isoform is compartmentalized in pancreatic β-cells and has a functional role in exocytosis [J].
Brown, H ;
Meister, B ;
Deeney, J ;
Corkey, BE ;
Yang, SN ;
Larsson, O ;
Rhodes, CJ ;
Seino, S ;
Berggren, PO ;
Fried, G .
DIABETES, 2000, 49 (03) :383-391
[3]   The subcellular localizations of atypical synaptotagmins III and VI -: Synaptotagmin III is enriched in synapses and synaptic plasma membranes but not in synaptic vesicles [J].
Butz, S ;
Fernandez-Chacon, R ;
Schmitz, F ;
Jahn, R ;
Südhof, TC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (26) :18290-18296
[4]   Synaptotagmin VII is targeted to dense-core vesicles and regulates their Ca2+-dependent exocytosis in PC12 cells [J].
Fukuda, M ;
Kanno, E ;
Satoh, M ;
Saegusa, C ;
Yamamoto, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (50) :52677-52684
[5]   RNA interference-mediated silencing of synaptotagmin IX, but not synaptotagmin I, inhibits dense-core vesicle exocytosis but not in PC12 cells [J].
Fukuda, M .
BIOCHEMICAL JOURNAL, 2004, 380 :875-879
[6]   Conserved N-terminal cysteine motif is essential for homo- and heterodimer formation of synaptotagmins III, V, VI, and X [J].
Fukuda, M ;
Kanno, E ;
Mikoshiba, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (44) :31421-31427
[7]   Alternative splicing isoforms of synaptotagmin VII in the mouse, rat and human [J].
Fukuda, M ;
Ogata, Y ;
Saegusa, C ;
Kanno, E ;
Mikoshiba, K .
BIOCHEMICAL JOURNAL, 2002, 365 (01) :173-180
[8]   Synaptotagmin IX regulates Ca2+-dependent secretion in PC12 cells [J].
Fukuda, M ;
Kowalchyk, JA ;
Zhang, XD ;
Martin, TFJ ;
Mikoshiba, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (07) :4601-4604
[9]  
FUKUDA M, 2003, RECENT RES DEV CHEM, V1, P15
[10]   Synaptotagmin III/VII isoforms mediate Ca2+-induced insulin secretion in pancreatic islet β-cells [J].
Gao, ZY ;
Reavey-Cantwell, J ;
Young, RA ;
Jegier, P ;
Wolf, BA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (46) :36079-36085