PI(3,5)P(2) controls membrane trafficking by direct activation of mucolipin Ca(2+) release channels in the endolysosome.
PI(3,5)P(2) controls membrane trafficking by direct activation of mucolipin Ca(2+) release channels in the endolysosome.
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DOI：
10.1038/ncomms1037
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发表时间：
2010-07-13
影响因子：
16.6
通讯作者：
Xu, Haoxing
中科院分区：
文献类型：
--
作者：
Dong, Xian-ping;Shen, Dongbiao;Wang, Xiang;Dawson, Taylor;Li, Xinran;Zhang, Qi;Cheng, Xiping;Zhang, Yanling;Weisman, Lois S.;Delling, Markus;Xu, Haoxing
胞内转运中的膜融合和分裂受胞内钙释放和肌醇磷脂信号的控制。然而，磷脂酰肌醇的钙释放通道和靶蛋白的分子同一性尚不清楚。在这里，通过直接膜片钳技术，我们报道了PI(3，5)P2，一种内溶酶体特异性的磷脂酰肌醇，结合并激活内溶酶体定位的粘蛋白Trp(TRPML)通道，具有特异性和有效性。PI(3，5)P2缺陷细胞和缺乏TRPML1的细胞都表现出内溶体/空泡增大和晚期内吞途径转运缺陷。我们发现，在PI(3，5)P2缺陷的小鼠成纤维细胞中观察到的扩大的空泡表型被TRPML1的过表达所抑制。值得注意的是，TRPML1的这种依赖于PI(3，5)P2的调节在进化上是保守的。在萌芽酵母中，高渗胁迫诱导液泡释放钙离子。在这里，我们表明，这个版本需要PI(3，5)P2生产和酵母功能TRPML同源物。我们认为，TRPMLS通过将PI(3，5)P2水平的信息转导到细胞器旁钙离子的变化来调节膜转运，从而触发膜融合/分裂事件。
Membrane fusion and fission in intracellular trafficking is controlled by both intraluminal Ca2+ release and phosphoinositide signaling. However, the molecular identities of the Ca2+ release channels and the target proteins of phosphoinositides are elusive. Here, by direct patch-clamping of the endolysosomal membrane, we report that PI(3,5)P2, an endolysosome-specific phosphoinositide, binds and activates endolysosome-localized mucolipin TRP (TRPML) channels with specificity and potency. Both PI(3,5)P2-deficient cells and cells that lack TRPML1 exhibited enlarged endolysosomes/vacuoles and trafficking defects in the late endocytic pathway. We find that the enlarged vacuole phenotype observed in PI(3,5)P2-deficient mouse fibroblasts is suppressed by overexpression of TRPML1. Notably, this PI(3,5)P2-dependent regulation of TRPML1 is evolutionarily conserved. In budding yeast, hyperosmotic stress induces Ca2+ release from the vacuole. Here, we show that this release requires both PI(3,5)P2 production and a yeast functional TRPML homolog. We propose that TRPMLs regulate membrane trafficking by transducing information about PI(3,5)P2 levels into changes in juxtaorganellar Ca2+, thereby triggering membrane fusion/fission events.
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影响因子：
4.7
作者：
Dong XP;Wang X;Xu H
通讯作者：
Xu H
DOI：
10.1073/pnas.141036198
发表时间：
2001-07-03
影响因子：
11.1
作者：
Palmer, CP;Zhou, XL;Saimi, Y
通讯作者：
Saimi, Y
DOI：
10.1073/pnas.0709846104
发表时间：
2007-12-04
影响因子：
11.1
作者：
Grimm, Christian;Cuajungco, Math P.;Heller, Stefan
通讯作者：
Heller, Stefan
影响因子：
2.5
作者：
Kim, Hee Seung;Kim, Jae Weon;Kang, Soon-Beom
通讯作者：
Kang, Soon-Beom
影响因子：
11.4
作者：
Nilius, Bernd;Owsianik, Grzegorz;Voets, Thomas
通讯作者：
Voets, Thomas