TRPML2 is an osmo/mechanosensitive cation channel in endolysosomal organelles.
TRPML2 is an osmo/mechanosensitive cation channel in endolysosomal organelles.
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DOI：
10.1126/sciadv.abb5064
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发表时间：
2020-11
期刊：
影响因子：
13.6
通讯作者：
Grimm C
中科院分区：
文献类型：
--
作者：
Chen CC;Krogsaeter E;Butz ES;Li Y;Puertollano R;Wahl-Schott C;Biel M;Grimm C
蛋白质运输由内体的微管/囊泡化介导，并受奥斯莫/机械敏感性TRPML 2调节。内溶体是动态的细胞内隔室，调节其表面与体积比以抵消由微管和囊泡形成事件后的渗透挑战引起的膜溶胀或收缩。虽然已广泛描述了质膜上的膜敏感性，但内溶酶体表面积与体积比变化的潜在机制和所涉及的离子通道的身份仍然难以捉摸。内溶体介导内吞作用、胞吐作用、货物运输和用于再循环或降解的材料分选。我们证明了内溶酶体阳离子通道TRPML 2是低渗/机械敏感的，这是其参与免疫细胞快速循环过程的关键特征。我们证明磷酸肌醇结合口袋是TRPML 2低渗敏感性所需的，因为L314的取代完全消除了低渗敏感性。最后，低渗不敏感的TRPML 2突变体L314 R减慢了快速循环途径，证实了低渗敏感的TRPML 2的功能重要性。我们的研究结果强调TRPML 2作为内溶酶体运输的加速剂，由于其低渗敏感性，在免疫细胞监视和病毒运输的影响。
Protein trafficking is mediated by tubulation/vesiculation of endosomes and is regulated by osmo/mechanosensitive TRPML2. Endolysosomes are dynamic, intracellular compartments, regulating their surface-to-volume ratios to counteract membrane swelling or shrinkage caused by osmotic challenges upon tubulation and vesiculation events. While osmosensitivity has been extensively described on the plasma membrane, the mechanisms underlying endolysosomal surface-to-volume ratio changes and identities of involved ion channels remain elusive. Endolysosomes mediate endocytosis, exocytosis, cargo transport, and sorting of material for recycling or degradation. We demonstrate the endolysosomal cation channel TRPML2 to be hypotonicity/mechanosensitive, a feature crucial to its involvement in fast-recycling processes of immune cells. We demonstrate that the phosphoinositide binding pocket is required for TRPML2 hypotonicity-sensitivity, as substitution of L314 completely abrogates hypotonicity-sensitivity. Last, the hypotonicity-insensitive TRPML2 mutant L314R slows down the fast recycling pathway, corroborating the functional importance of hypotonicity-sensitive TRPML2. Our results highlight TRPML2 as an accelerator of endolysosomal trafficking by virtue of its hypotonicity-sensitivity, with implications in immune cell surveillance and viral trafficking.
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DOI：
10.1016/j.bbamcr.2018.10.020
发表时间：
2019-07
期刊：
Biochimica et biophysica acta. Molecular cell research
影响因子：
--
作者：
Krogsaeter EK;Biel M;Wahl-Schott C;Grimm C
通讯作者：
Grimm C
DOI：
10.4049/jimmunol.1500163
发表时间：
2015-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
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通讯作者：
Puertollano R
影响因子：
8.6
作者：
Chen, Cheng-Chang;Butz, Elisabeth S.;Grimm, Christian
通讯作者：
Grimm, Christian
影响因子：
7.7
作者：
Plesch E;Chen CC;Butz E;Scotto Rosato A;Krogsaeter EK;Yinan H;Bartel K;Keller M;Robaa D;Teupser D;Holdt LM;Vollmar AM;Sippl W;Puertollano R;Medina D;Biel M;Wahl-Schott C;Bracher F;Grimm C
通讯作者：
Grimm C
DOI：
10.1073/pnas.1705739114
发表时间：
2017-10-10
影响因子：
11.1
作者：
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通讯作者：
Grimm, Christian