Mouse trp2 the homologue of the human trpc2 pseudogene encodes mTrp2 a store depletion-activated capacitative Ca2+ entry channel

摘要

Capacitative Ca²⁺ entry (CCE) is Ca²⁺ entering after stimulation of inositol 1,4,5-trisphosphate (IP3) formation and initiation of Ca²⁺ store depletion. One hallmark of CCE is that it can also be triggered merely by store depletion, as occurs after inhibition of internal Ca²⁺ pumps with thapsigargin. Evidence has accumulated in support of a role of transient receptor potential (Trp) proteins as structural subunits of a class of Ca²⁺-permeable cation channels activated by agonists that stimulate IP3 formation—very likely through a direct interaction between the IP3 receptor and a Trp subunit of the Ca²⁺ entry channel. The role of Trp’s in Ca²⁺ entry triggered by store depletion alone is less clear. Only a few of the cloned Trp’s appear to enhance this type of Ca²⁺ entry, and when they do, the effect requires special conditions to be observed, which native CCE does not. Here we report the full-length cDNA of mouse trp2, the homologue of the human trp2 pseudogene. Mouse Trp2 is shown to be readily activated not only after stimulation with an agonist but also by store depletion in the absence of an agonist. In contrast to other Trp proteins, Trp2-mediated Ca²⁺ entry activated by store depletion is seen under the same conditions that reveal endogenous store depletion-activated Ca²⁺ entry, i.e., classical CCE. The findings support the general hypothesis that Trp proteins are subunits of store- and receptor-operated Ca²⁺ channels.