A C-terminally truncated mouse Best3 splice variant targets and alters the ion balance in lysosome-endosome hybrids and the endoplasmic reticulum.
A C-terminally truncated mouse Best3 splice variant targets and alters the ion balance in lysosome-endosome hybrids and the endoplasmic reticulum.
复制标题
C端截短的小鼠Best3剪接变体靶向并改变溶酶体-内体杂合体和内质网中的离子平衡
DOI：
10.1038/srep27332
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发表时间：
2016-06-06
影响因子：
4.6
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Wu L;Sun Y;Ma L;Zhu J;Zhang B;Pan Q;Li Y;Liu H;Diao A;Li Y
Bestrophin家族在哺乳动物中被描述为Cl−通道，在细菌中被描述为Na+通道，但它们确切的生理作用仍然未知。在这项研究中，小鼠Bestrophin 3（Best 3V 2）在成肌细胞和肌肉中表达的天然C-末端截短变体被证明。与全长Best 3不同，Best 3V 2靶向两个重要的细胞内钙库：溶酶体和ER。异源胞苷过度表达导致溶酶体肿胀并使其酸性降低。Best 3V 2过表达还导致从ER释放的Ca 2+受损。敲低成肌细胞中的内源性Best 3表达使这些细胞对Ca 2+动员试剂（如咖啡因）的反应更兴奋。我们建议，Best 3V 2在成肌细胞可能作为一个调谐器，以控制从细胞内钙库释放钙。
The Bestrophin family has been characterized as Cl− channels in mammals and Na+ channels in bacteria, but their exact physiological roles remian unknown. In this study, a natural C-terminally truncated variant of mouse Bestrophin 3 (Best3V2) expression in myoblasts and muscles is demonstrated. Unlike full-length Best3, Best3V2 targets the two important intracellular Ca stores: the lysosome and the ER. Heterologous overexpression leads to lysosome swelling and renders it less acidic. Best3V2 overexpression also results in compromised Ca2+ release from the ER. Knocking down endogenous Best3 expression in myoblasts makes these cells more excitable in response to Ca2+ mobilizing reagents, such as caffeine. We propose that Best3V2 in myoblasts may work as a tuner to control Ca2+ release from intracellular Ca2+ stores.