Identity revealed for a long-sought ER anion channel.
Identity revealed for a long-sought ER anion channel.
复制标题
揭示了长期以来寻找的 ER 阴离子通道的身份。
DOI：
10.1038/s41422-023-00807-1
复制
发表时间：
2023
期刊：
影响因子：
44.1
通讯作者：
Bianchi,Laura
中科院分区：
文献类型：
--
作者：
Bianchi,Laura
Ca 2+从内质网（ER）释放需要平衡离子的流动。在最近发表在Cell Research上的一篇论文中，Guo及其同事使用强大的组合方法表明，CLCC 1是长期以来一直在寻找的Cl-从ER流出的介质，其抵消Ca 2+释放，并且其损失导致ER应激并有助于ALS病理学。内质网（ER）是除成熟红细胞外的所有真核细胞中发现的细胞内膜网络。ER具有许多功能。它是跨膜和分泌蛋白的生物合成和折叠的位点，它是蛋白修饰如糖基化和切割发生的地方，并且它是类固醇激素和磷脂合成的位点。ER也是细胞内Ca 2+浓度的调节剂。Ca 2+是许多生理功能的关键离子，从兴奋性、分泌和收缩到调节许多细胞溶质和膜蛋白的功能。因此，Ca 2+稳态的精确调节具有重要的生理后果，其失调可导致疾病。Ca ~（2+）通过兰尼碱受体（RyR）和肌醇1，4，5-三磷酸受体（IP 3R）从ER释放，并通过肌/内质网Ca ~（2+）-ATP酶（SERCA）摄取。Ca ~（2+）跨内质网膜的运动是产电的。例如，从ER释放的Ca 2+倾向于在反式室中积累负电荷，这阻碍了进一步的Ca 2+释放。因此，必须存在平衡离子通量的介质来中和这种电荷积累。
Ca2+ release from the endoplasmic reticulum (ER) requires flux of counterions. In a recent paper published in Cell Research, Guo and colleagues, using a powerful combinatorial approach, show that CLCC1 is the long-sought mediator of Cl–efflux from the ER that counteracts Ca2+ release and that its loss causes ER stress and contributes to ALS pathology.The endoplasmic reticulum (ER) is a network of intracellular membranes found in all eukaryotic cells except for mature red blood cells. The ER has many functions. It is the site of biosynthesis and folding of transmembrane and secreted proteins, it is where protein modifications such as glycosylation and cleavage occur, and it is the site of steroid hormone and phospholipid synthesis. The ER is also a regulator of intracellular Ca2+ concentration. Ca2+ is a key ion in many physiological functions from excitability, secretion, and contraction to regulation of the function of many cytosolic and membrane proteins. Thus, precise regulation of Ca2+ homeostasis has important physiological consequences, and its dysregulation can lead to disease. Ca2+ is released from the ER via ryanodine receptors (RyRs) and inositol 1, 4, 5-trisphosphate receptors (IP3Rs) and is taken up via the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). The movement of Ca2+ across the ER membrane is electrogenic. For example, Ca2+ release from the ER tends to accumulate negative charges in the trans compartment, which impedes further Ca2+ release. Thus, mediators for the flux of counterions must exist to neutralize this charge accumulation.