Sugawara H, Kurosaki M, Takata M, Kurosaki T
Department of Integrated Medicine, Omiya Medical Center, Jichi Medical School, Japan.
EMBO J. 1997 Jun 2;16(11):3078-88. doi: 10.1093/emboj/16.11.3078.
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 (IP3Rs) 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 in 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 IP3Rs 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.
B细胞抗原受体（BCR）的刺激会导致细胞质游离钙迅速增加，这是由于钙从细胞内储存库释放以及从细胞外环境流入。肌醇1,4,5-三磷酸受体（IP3Rs）是配体门控通道，可响应第二信使肌醇1,4,5-三磷酸释放细胞内钙储存。包括B细胞在内的大多数造血细胞表达三种不同类型IP3R中的至少两种。我们在此证明，单一类型IP3R被缺失的B细胞在BCR刺激下仍能动员钙，但缺乏所有三种类型IP3R的B细胞中的这种钙动员被消除。转染的G蛋白偶联受体（毒蕈碱M1受体）介导的钙动员也仅在三重缺陷细胞中被消除。毒胡萝卜素刺激的容量性Ca2+内流不受所有三种类型IP3R缺失的影响。这些数据表明，IP3Rs是BCR和毒蕈碱受体诱导的钙动员的必需且功能冗余的介质，但不是毒胡萝卜素诱导的Ca2+内流的介质。我们进一步表明，所有三种类型IP3R的缺失会显著抑制BCR诱导的细胞凋亡，这表明Ca2+在细胞凋亡过程中起重要作用。
