STIM1 is a MT-plus-end-tracking protein involved in remodeling of the ER
STIM1 is a MT-plus-end-tracking protein involved in remodeling of the ER
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DOI：
10.1016/j.cub.2007.12.050
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发表时间：
2008-02-12
期刊：
影响因子：
9.2
通讯作者：
Akhmanova, Anna
中科院分区：
文献类型：
--
作者：
Grigoriev, Ilya;Gouveia, Susana Montenegro;Akhmanova, Anna
基质相互作用分子1(STIM1)是一种跨膜蛋白，是细胞外钙(2+)内流的过程，对内质网(ER)内的钙(2+)储备的耗竭做出反应(见文献[1-4])。STIM1主要定位于内质网；当钙离子从内质网释放后，STIM1转位到内质网-质膜连接并激活钙通道(见文献[1-4])。在这里，我们证明了STIM1直接与微管+末端跟踪蛋白EB1结合，并在聚合微管末端与ER网络接触的位置形成依赖于EB1的彗星样堆积。因此，先前观察到的GFP-STIM1[5]的管腔运动不是一种基于运动的运动，而是内质网中STIM1浓度的扩散依赖的行波。STIM1的过度表达强烈地刺激内质网延伸发生在微管的“末端附着复合体”(TAC)机制[6，7]，在这个过程中，内质网小管附着在生长中的微管的EB1阳性端并与其一起延伸。STIM1和EB1的缺失减少了TAC依赖的ER突起，表明微管生长依赖的STIM1在ER膜上的浓度在ER重塑中起作用。
Stromal interaction molecule 1 (STIM1) is a transmembrane protein that is essential for store-operated Ca(2+) entry, a process of extracellular Ca(2+) influx in response to the depletion of Ca(2+) stores in the endoplasmic reticulum (ER) (reviewed in [1-4]). STIM1 localizes predominantly to the ER; upon Ca(2+) release from the ER, STIM1 translocates to the ER-plasma membrane junctions and activates Ca2+ channels (reviewed in [1-4]). Here, we show that STIM1 directly binds to the microtubule-plus-end-tracking protein EB1 and forms EB1-dependent comet-like accumulations at the sites where polymerizing microtubule ends come in contact with the ER network. Therefore, the previously observed tubulovesicular motility of GFP-STIM1 [5] is not a motor-based movement but a traveling wave of diffusion-dependent STIM1 concentration in the ER membrane. STIM1 overexpression strongly stimulates ER extension occurring through the microtubule "tip attachment complex" (TAC) mechanism [6, 7], a process whereby an ER tubule attaches to and elongates together with the EB1-positive end of a growing microtubule. Depletion of STIM1 and EB1 decreases TAC-dependent ER protrusion, indicating that microtubule growth-dependent concentration of STIM1 in the ER membrane plays a role in ER remodeling.