Deviant lysosomal K+ fluxes and Parkinson's. A calci-centric point of view.
Deviant lysosomal K+ fluxes and Parkinson's. A calci-centric point of view.
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DOI：
10.1016/j.ceca.2021.102418
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发表时间：
2021-05
期刊：
影响因子：
4
通讯作者：
Martina Gregori;S. Bolsover;S. Patel
中科院分区：
文献类型：
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作者：
Martina Gregori;S. Bolsover;S. Patel
TMEM175 是一种与帕金森病相关的溶酶体 K+ 通道，但对其调控方式知之甚少。 Wie 等人描述了 TMEM175 中的致病变异，将通道活性与帕金森病风险相关联，并揭示了 AKT 在门控中的新型激酶独立作用。溶酶体腔是 H+ 以及 Ca2+、Na+ 和其他离子（如 Fe2+ 和 Zn2+）的浓缩物 (1)。遍布整个溶酶体膜的泵、离子通道和转运蛋白支持电流，从而设定溶酶体膜电位并调节胞质 Ca2+ 水平 (1)。该生物回路的故障导致溶酶体形态缺陷、自噬受损和囊泡运输失调，并与多种疾病相关 (1)。
TMEM175 is a lysosomal K+ channel linked to Parkinson’s but little is known on how it is regulated. Wie et al characterised pathogenic variants in TMEM175, correlated channel activity with Parkinson’s risk and revealed a novel kinase-independent role for AKT in gating.The lysosomal lumen is a concentrate of H+ together with Ca2+, Na+ and other ions such as Fe2+ and Zn2+(1). Pumps, ion channels and transporters peppered throughout the lysosomal membrane support currents that set the lysosomal membrane potential and regulate cytosolic Ca2+ levels (1). Failures in this biological circuit underpin lysosomal morphology defects, impaired autophagy and deregulated vesicle trafficking, and have been associated with several diseases (1).