One of the most rapid (less than 4 ms) transmembrane cellular mechanotransduction events involves activation of transient receptor potential vanilloid 4 (TRPV4) ion channels by mechanical forces transmitted across cell surface β1 integrin receptors on endothelial cells, and the transmembrane solute carrier family 3 member 2 (herein denoted CD98hc, also known as SLC3A2) protein has been implicated in this response. Here, we show that β1 integrin, CD98hc and TRPV4 all tightly associate and colocalize in focal adhesions where mechanochemical conversion takes place. CD98hc knockdown inhibits TRPV4-mediated calcium influx induced by mechanical forces, but not by chemical activators, thus confirming the mechanospecificity of this signaling response. Molecular analysis reveals that forces applied to β1 integrin must be transmitted from its cytoplasmic C terminus via the CD98hc cytoplasmic tail to the ankyrin repeat domain of TRPV4 in order to produce ultrarapid, force-induced channel activation within the focal adhesion.

最快速（小于 4 ms）的跨膜细胞机械转导事件之一涉及通过内皮细胞上的细胞表面 β1 整合素受体和跨膜溶质载体家族 3 成员传递的机械力激活瞬时受体电位香草酸 4 (TRPV4) 离子通道2（本文表示为 CD98hc，也称为 SLC3A2）蛋白参与了这种反应。在这里，我们发现 β1 整合素、CD98hc 和 TRPV4 都紧密关联并共定位于发生机械化学转化的粘着斑中。CD98hc 敲除抑制机械力诱导的 TRPV4 介导的钙内流，但不抑制化学激活剂诱导的钙内流，从而证实了这种信号反应的机械特异性。分子分析表明，施加到 β1 整合素的力必须从其细胞质 C 末端通过 CD98hc 细胞质尾部传递到 TRPV4 的锚蛋白重复结构域，以便在粘着斑内产生超快速、力诱导的通道激活。