Mouse trp2, the homologue of the human trpc2 pseudogene, encodes mTrp2, a store depletion-activated capacitative Ca2+ entry channel.
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.
Department of Anesthesiology, University of California, Los Angeles, CA 90095, USA.
B
B
Vannier
M
M
Peyton
G
G
Boulay
D
D
Brown
N
N
Qin
M
M
Jiang
X
X
Zhu
L
L
Birnbaumer
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary; D011544:Pseudogenes; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels; D013737:Testis / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection
D015220:Calcium Channels; D007473:Ion Channels; D008565:Membrane Proteins; D011994:Recombinant Proteins; D050052:TRPC Cation Channels; C491859:TRPC2 protein, human; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; C113139:Trp2 protein, vertebrate; C491858:Trpc2 protein, mouse; D019284:Thapsigargin; D002118:Calcium