Canonical transient receptor potential 5 channel in conjunction with Orai1 and STIM1 allows Sr2+ entry, optimal influx of Ca2+, and degranulation in a rat mast cell line

被引：75

作者：

Ma, Hong-Tao ^{[1
]}

Peng, Ze ^{[1
]}

Hiragun, Takaaki ^{[1
]}

Iwaki, Shoko ^{[2
]}

Gilfillan, Alasdair M. ^{[2
]}

Beaven, Michael A. ^{[1
]}

机构：

[1] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA

[2] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA

来源：

JOURNAL OF IMMUNOLOGY | 2008年 / 180卷 / 04期

关键词：

D O I：

10.4049/jimmunol.180.4.2233

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Degranulation of mast cells in response to Ag or the calcium mobilizing agent, thapsigargin, is dependent on emptying of intracellular stores of Ca2+ and the ensuing influx of external Ca2+, also referred to as store-operated calcium entry. However, it is unlikely that the calcium release-activated calcium channel is the sole mechanism for the entry of Ca2+ because Sr2+ and other 14 divalent cations also permeate and support degranulation in stimulated mast cells. In this study we show that influx of Ca2+ and Sr2+ as well as degranulation are dependent on the presence of the canonical transient receptor potential (TRPC) channel protein TRPC5, in addition to STIM1 and Orai1, as demonstrated by knock down of each of these proteins by inhibitory RNAs in a rat mast cell (RBL-2H3) line. Overexpression of STIM1 and Orai1, which are known to be essential components of calcium release-activated calcium channel, allows entry of Ca2+ but not Sr2+ whereas overexpression of STIM1 and TRPC5 allows entry of both Ca2+ and Sr2+. These and other observations suggest that the Sr2+-permeable TRPC5 associates with STIM1 and Orai1 in a stoichiometric manner to enhance entry of Ca2+ to generate a signal for degranulation.

引用

页码：2233 / 2239

页数：7

共 68 条

[1] ANTIGEN AND THAPSIGARGIN PROMOTE INFLUX OF CA2+ IN RAT BASOPHILIC RBL-2H3 CELLS BY OSTENSIBLY SIMILAR MECHANISMS THAT ALLOW FILLING OF INOSITOL 1,4,5-TRISPHOSPHATE-SENSITIVE AND MITOCHONDRIAL CA2+ STORES [J].