Genetic evidence for involvement of type 1, type 2 and type 3 inositol 1,4,5-trisphosphate receptors in signal transduction through the B-cell antigen receptor

被引:371
作者
Sugawara, H
Kurosaki, M
Takata, M
Kurosaki, T
机构
[1] JICHI MED SCH,OMIYA MED CTR,DEPT INTEGRATED MED,OMIYA,SAITAMA 330,JAPAN
[2] KANSAI MED UNIV,DEPT MOL GENET,INST HEPAT RES,MORIGUCHI,OSAKA 570,JAPAN
[3] KYOTO UNIV,GRAD SCH MED,DEPT MOL IMMUNOL & ALLERGY,KYOTO 60601,JAPAN
关键词
apoptosis; B-cell antigen receptor; calcium mobilization; inositol 1,4,5-trisphosphate receptor; muscarinic receptor;
D O I
10.1093/emboj/16.11.3078
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
Stimulation of B-cell antigen receptor (BCR) induces a rapid increase in cytoplasmic free calcium due to its release from intracellular stores and influx from the extracellular environment. Inositol 1,4,5-trisphosphate receptors (IP(3)Rs) are ligand-gated channels that release intracellular calcium stores in response to the second messenger, inositol 1,4,5-trisphosphate. Most hematopoietic cells, including B cells, express at least two of the three different types of IP3R. We demonstrate here that B cells in which a single type of IP3R has been deleted still mobilize calcium in response to BCR stimulation, whereas this calcium mobilization is abrogated hi B cells lacking all three types of IP3R. Calcium mobilization by a transfected G protein-coupled receptor (muscarinic M1 receptor) was also abolished in only triple-deficient cells, Capacitative Ca2+ entry, stimulated by thapsigargin, remains unaffected by loss of all three types of IP3R. These data establish that IP(3)Rs are essential and functionally redundant mediators for both BCR- and muscarinic receptor-induced calcium mobilization, but not for thapsigargin-induced Ca2+ influx. We further show that the BCR-induced apoptosis is significantly inhibited by loss of all three types of IP3R, suggesting an important role for Ca2+ in the process of apoptosis.
引用
收藏
页码:3078 / 3088
页数:11
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