Mutant IP3 receptors attenuate store-operated Ca2+ entry by destabilizing STIM-Orai interactions in Drosophila neurons.
Mutant IP3 receptors attenuate store-operated Ca2+ entry by destabilizing STIM-Orai interactions in Drosophila neurons.
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DOI：
10.1242/jcs.191585
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发表时间：
2016-10-15
影响因子：
4
通讯作者：
Hasan G
中科院分区：
文献类型：
--
作者：
Chakraborty S;Deb BK;Chorna T;Konieczny V;Taylor CW;Hasan G
当内质网（ER）中Ca 2+的丢失刺激Ca 2+传感器STIM聚集并激活质膜Ca 2+通道奥赖（在果蝇中由Olf 186-F编码）时，发生钙库操纵的Ca 2+内流（SOCE）。肌醇1，4，5-三磷酸受体（IP 3Rs）是由果蝇中的一个单基因编码的，被认为仅通过介导内质网Ca ~（2+）的释放来调节SOCE。我们发现，在果蝇神经元中，突变IP 3R减弱SOCE引起的消耗Ca 2+商店与毒胡萝卜素。在正常神经元中，储存耗尽导致STIM和IP 3 R在质膜附近积聚，STIM与奥赖结合，STIM和奥赖在ER-质膜连接处聚集以及SOCE激活。这些反应在具有突变型IP 3受体的神经元中减弱，并且通过用奥赖过表达STIM来拯救。我们的结论是，耗尽后的Ca 2+商店在果蝇，易位的IP 3 R ER-质膜连接促进耦合STIM奥赖，导致激活的SOCE。总结：在果蝇神经元中，突变型IP 3受体通过STIM与Ca 2+通道奥赖的不稳定相互作用破坏钙池操作的Ca 2+内流。这种相互作用可以协调钙库排空和钙内流。
Store-operated Ca2+ entry (SOCE) occurs when loss of Ca2+ from the endoplasmic reticulum (ER) stimulates the Ca2+ sensor, STIM, to cluster and activate the plasma membrane Ca2+ channel Orai (encoded by Olf186-F in flies). Inositol 1,4,5-trisphosphate receptors (IP3Rs, which are encoded by a single gene in flies) are assumed to regulate SOCE solely by mediating ER Ca2+ release. We show that in Drosophila neurons, mutant IP3R attenuates SOCE evoked by depleting Ca2+ stores with thapsigargin. In normal neurons, store depletion caused STIM and the IP3R to accumulate near the plasma membrane, association of STIM with Orai, clustering of STIM and Orai at ER–plasma-membrane junctions and activation of SOCE. These responses were attenuated in neurons with mutant IP3Rs and were rescued by overexpression of STIM with Orai. We conclude that, after depletion of Ca2+ stores in Drosophila, translocation of the IP3R to ER–plasma-membrane junctions facilitates the coupling of STIM to Orai that leads to activation of SOCE. Summary: In Drosophila neurons, mutant IP3 receptors disrupt store-operated Ca2+ entry by destabilizing interaction of STIM with the Ca2+ channel, Orai. The interactions could coordinate store emptying with Ca2+ entry.
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影响因子：
64.5
作者：
Park CY;Hoover PJ;Mullins FM;Bachhawat P;Covington ED;Raunser S;Walz T;Garcia KC;Dolmetsch RE;Lewis RS
通讯作者：
Lewis RS
DOI：
10.1126/science.1228757
发表时间：
2012-12-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hou X;Pedi L;Diver MM;Long SB
通讯作者：
Long SB
DOI：
10.1073/pnas.0902982106
发表时间：
2009-06-23
影响因子：
11.1
作者：
Venkiteswaran, Gayatri;Hasan, Gaiti
通讯作者：
Hasan, Gaiti
影响因子：
16.6
作者：
Deb BK;Pathak T;Hasan G
通讯作者：
Hasan G
DOI：
10.1016/j.cub.2009.08.022
发表时间：
2009-11-03
期刊：
Current biology : CB
影响因子：
--
作者：
Bird GS;Hwang SY;Smyth JT;Fukushima M;Boyles RR;Putney JW Jr
通讯作者：
Putney JW Jr