Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar.
J Cell Physiol. 2013 Dec;228(12):2386-98. doi: 10.1002/jcp.24411.
The TRP gene family encodes primarily cation non-selective, Ca2+ permeant channels that are involved in a dizzying array of sensory mechanisms. Two channels in this large family TRPV5 and TRPV6 are highly Ca2+ selective and are expressed in epithelia where they are important in Ca2+ uptake. TRPV5/6 are constitutively active, yet the mechanisms regulating their activation in native tissue remains elusive. Here we functionally characterize the Xenopus TRPV6 homolog. xTRPV6 is expressed in the oocyte and encodes a channel that is permeant to divalents including Ca2+ , and displays a high permeability to Mg2+ . The oocyte does not exhibit functional TRPV6-like current at rest, showing that the endogenous channel is somehow maintained in an inactive state. We show that endogenous as well as overexpressed xTRPV6 interacts with xTRPC1 and that this interaction inhibits xTRPV6 currents. As such TRPC1 is likely to regulate the activity of TRPV6 under physiological conditions.
TRP 基因家族编码主要的阳离子非选择性、Ca2+渗透性通道，这些通道参与了令人眼花缭乱的各种感觉机制。这个大家族中的两个通道 TRPV5 和 TRPV6 对 Ca2+具有高度选择性，并在表达于上皮组织中，在那里它们对 Ca2+摄取很重要。TRPV5/6 是组成型激活的，然而，在天然组织中调节其激活的机制仍然难以捉摸。在这里，我们对非洲爪蟾 TRPV6 同源物进行了功能表征。xTRPV6 在卵母细胞中表达，并编码一种对二价离子包括 Ca2+具有渗透性的通道，并对 Mg2+显示出高渗透性。卵母细胞在静息时不表现出功能性 TRPV6 样电流，表明内源性通道以某种方式保持在非活跃状态。我们表明，内源性和过表达的 xTRPV6 与 xTRPC1 相互作用，这种相互作用抑制了 xTRPV6 电流。因此，TRPC1 很可能在生理条件下调节 TRPV6 的活性。
