Cellular defects by deletion of ANO10 are due to deregulated local calcium signaling

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• 作者：Podchanart Wanitchakool ; Jiraporn Ousingsawat ; Lalida Sirianant ; Inê ; s Cabrita ; Diana Faria ; Rainer Schreiber¹ ; Karl Kunzelmann ; ¹ ; ^{karl.kunzelmann@ur.de}
• 关键词：TMEM16K ; Anoctamin 10 ; ANO10 ; Apoptosis ; Ca2  ; + signaling ; Ion channels ; Jejunum ; Macrophages
• 刊名：Cellular Signalling
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：30
• 期：Complete
• 页码：41-49
• 全文大小：1673 K
• 卷排序：30

文摘

TMEM16K (anoctamin 10; ANO10) belongs to a putative family of ion channels and membrane phospholipid scramblases. Mutations in ANO10 cause neurological and immunological defects, and abrogate ion transport. We demonstrate that knockout of ANO10 in animals and in vitro induces various cellular defects. Most remarkably, spontaneous and TNF-induced apoptosis is almost abolished after knockout of ANO10. The data demonstrate functional similarity with Axs, the Drosophila ortholog of ANO10. A pathogenic principle is suggested, based on deranged local Ca2 + signaling leading to cellular dysfunctions and neurological disorders such as ataxia. The present results have implications for the therapy of ataxia and other neurological disorders, as idebenone, a drug commonly used in ataxia, is an inhibitor of anoctamins.