STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx

被引:1810
作者
Liou, J [1 ]
Kim, ML [1 ]
Heo, WD [1 ]
Jones, JT [1 ]
Myers, JW [1 ]
Ferrell, JE [1 ]
Meyer, T [1 ]
机构
[1] Stanford Univ, Sch Med, Dept Mol Pharmacol, Stanford, CA 94305 USA
关键词
D O I
10.1016/j.cub.2005.05.055
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
Ca2+ signaling in nonexcitable cells is typically initiated by receptor-triggered production of inositol-1,4,5-tris-phosphate and the release of Ca2+ from intracellular stores [1]. An elusive signaling process senses the Ca2+ store depletion and triggers the opening of plasma membrane Ca2+ channels [2-5]. The resulting sustained Ca2+ signals are required for many physiological responses, such as T cell activation and differentiation [6]. Here, we monitored receptor-triggered Ca2+ signals in cells transfected with siRNAs against 2,304 human signaling proteins, and we identified two proteins required for Ca2+-store-depletion-mediated Ca2+ influx, STIM1 and STIM2 [7-9]. These proteins have a single transmembrane region with a putative Ca2+ binding domain in the lumen of the endoplasmic reticulum. Ca2+ store depletion led to a rapid translocation of STIM1 into puncta that accumulated near the plasma membrane. Introducing a point mutation in the STIM1 Ca2+ binding domain resulted in prelocalization of the protein in puncta, and this mutant failed to respond to store depletion. Our study suggests that STIM proteins function as Ca2+ store sensors in the signaling pathway connecting Ca2+ store depletion to Ca2+ influx.
引用
收藏
页码:1235 / 1241
页数:7
相关论文
共 25 条
[11]   Stimulation by thimerosal of histamine-induced Ca2+ release in intact HeLa cells seen with aequorin targeted to the endoplasmic reticulum [J].
Montero, M ;
Barrero, MJ ;
Torrecilla, F ;
Lobatón, CD ;
Moreno, A ;
Alvarez, J .
CELL CALCIUM, 2001, 30 (03) :181-190
[12]   Recombinant Dicer efficiently converts large dsRNAs into siRNAs suitable for gene silencing [J].
Myers, JW ;
Jones, JT ;
Meyer, T ;
Ferrell, JE .
NATURE BIOTECHNOLOGY, 2003, 21 (03) :324-328
[13]   Identification of stromal cell products that interact with pre-B cells [J].
Oritani, K ;
Kincade, PW .
JOURNAL OF CELL BIOLOGY, 1996, 134 (03) :771-782
[14]   Molecular cloning of a novel human gene (D11S4896E) at chromosomal region 11p15.5 [J].
Parker, NJ ;
Begley, CG ;
Smith, PJ ;
Fox, RM .
GENOMICS, 1996, 37 (02) :253-256
[15]   CRAC channels: activation, permeation, and the search for a molecular identity [J].
Prakriya, M ;
Lewis, RS .
CELL CALCIUM, 2003, 33 (5-6) :311-321
[16]  
Putney J W Jr, 2001, Mol Interv, V1, P84
[17]   A MODEL FOR RECEPTOR-REGULATED CALCIUM ENTRY [J].
PUTNEY, JW .
CELL CALCIUM, 1986, 7 (01) :1-12
[18]  
Putney JW, 2001, J CELL SCI, V114, P2223
[19]   STIM1, an essential and conserved component of store-operated Ca2+ channel function [J].
Roos, J ;
DiGregorio, PJ ;
Yeromin, AV ;
Ohlsen, K ;
Lioudyno, M ;
Zhang, SY ;
Safrina, O ;
Kozak, JA ;
Wagner, SL ;
Cahalan, MD ;
Veliçelebi, G ;
Stauderman, KA .
JOURNAL OF CELL BIOLOGY, 2005, 169 (03) :435-445
[20]  
Sabbioni S, 1997, CANCER RES, V57, P4493