Instituto de Medicina Molecular, Faculdade de Medicina , Universidade de Lisboa , Avenida Professor Egas Moniz , 1649-028 Lisboa , Portugal.
Department of Chemistry , University of Cambridge , Lensfield Road , Cambridge CB2 1EW , U.K.
Biochemistry. 2019 Jul 2;58(26):2861-2866. doi: 10.1021/acs.biochem.9b00224. Epub 2019 Jun 20.
The recent discovery of the osmosensitive calcium (Ca) channel OSCA has revealed the potential mechanism by which plant cells sense diverse stimuli. Osmosensory transporters and mechanosensitive channels can detect and respond to osmotic shifts that play an important role in active cell homeostasis. Members of the TMEM63 family of proteins are described as the closest homologues of OSCAs. Here, we characterize TMEM63B, a mammalian homologue of OSCAs, recently classified as mechanosensitive. In HEK293T cells, TMEM63B localizes to the plasma membrane and is associated with F-actin. This Ca-permeable channel specifically induces Ca influx across the membrane in response to extracellular Ca concentration and hyperosmolarity. In addition, overexpression of TMEM63B in HEK293T cells significantly enhanced cell migration and wound healing. The link between Ca osmosensitivity and cell migration might help to establish TMEM63B's pathogenesis, for example, in cancer in which it is frequently overexpressed.
最近发现的渗透压敏感钙（Ca）通道 OSCA 揭示了植物细胞感知各种刺激的潜在机制。渗透感受器转运蛋白和机械敏感通道可以检测和响应渗透压变化，这些变化在细胞主动稳态中起着重要作用。TMEM63 家族的蛋白被描述为 OSCAs 的最接近的同源物。在这里，我们对 TMEM63B 进行了表征，TMEM63B 是 OSCAs 的哺乳动物同源物，最近被归类为机械敏感。在 HEK293T 细胞中，TMEM63B 定位于质膜并与 F-肌动蛋白相关。这种 Ca 通透性通道特异性地诱导膜对细胞外 Ca 浓度和高渗的 Ca 内流。此外，在 HEK293T 细胞中转染 TMEM63B 可显著增强细胞迁移和伤口愈合。Ca 渗透压敏感性与细胞迁移之间的联系可能有助于建立 TMEM63B 的发病机制，例如在癌症中，TMEM63B 经常过度表达。
