The role of canonical transient receptor potential 7 in B-cell receptor-activated channels.
Phospholipase C signaling stimulates Ca2+ entry across the plasma membrane through multiple mechanisms. Ca2+ store depletion stimulates store-operated Ca2+-selective channels, or alternatively, other phospholipase C-dependent events activate Ca2+-permeable non-selective cation channels. Transient receptor potential 7 (TRPC7) is a non-selective cation channel that can be activated by both mechanisms when ectopically expressed, but the regulation of native TRPC7 channels is not known. We knocked out TRPC7 in DT40 B-cells, which expresses both forms of Ca2+ entry. No difference in the store-operated current I(crac) was detected between TRPC7-/- and wild-type cells. Wild-type cells demonstrated nonstore-operated cation entry and currents in response to activation of the B-cell receptor or protease-activated receptor 2, intracellular dialysis with GTPgammaS, or application of the synthetic diacylglycerol oleyl-acetyl-glycerol. These responses were absent in TRPC7-/- cells but could be restored by transfection with human TRPC7. In conclusion, in B-lymphocytes, TRPC7 appeared to participate in the formation of ion channels that could be activated by phospholipase C-linked receptors. This represents the first demonstration of a physiological function for endogenous TRPC7 channels.
Lievremont
Jean-Philippe
JP
Department of Health and Human Services, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Numaga
Takuro
T
Vazquez
Guillermo
G
Lemonnier
Loïc
L
Hara
Yuji
Y
Mori
Emiko
E
Trebak
Mohamed
M
Moss
Stephen E
SE
Bird
Gary S
GS
Mori
Yasuo
Y
Putney
James W
JW
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001464:Barium / Q000378:metabolism; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry; D002412:Cations; D002460:Cell Line; D002645:Chickens; D004075:Diglycerides / Q000737:chemistry; D004594:Electrophysiology; D005990:Glycerol / Q000737:chemistry; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000737:chemistry; D007477:Ions; D008957:Models, Genetic; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D050052:TRPC Cation Channels / Q000378:metabolism / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D019076:Transgenes; D010738:Type C Phospholipases / Q000378:metabolism*
D015220:Calcium Channels; D002412:Cations; D004075:Diglycerides; D007473:Ion Channels; D007477:Ions; D011947:Receptors, Antigen, B-Cell; D050052:TRPC Cation Channels; C498501:TRPC7 protein, human; D001464:Barium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019284:Thapsigargin; D010738:Type C Phospholipases; D005990:Glycerol; D002118:Calcium