Ca2+ influx and protein scaffolding via TRPC3 sustain PKCbeta and ERK activation in B cells.
Ca(2+) signaling mediated by phospholipase C that produces inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] and diacylglycerol (DAG) controls lymphocyte activation. In contrast to store-operated Ca(2+) entry activated by Ins(1,4,5)P(3)-induced Ca(2+) release from endoplasmic reticulum, the importance of DAG-activated Ca(2+) entry remains elusive. Here, we describe the physiological role of DAG-activated Ca(2+) entry channels in B-cell receptor (BCR) signaling. In avian DT40 B cells, deficiency of transient receptor potential TRPC3 at the plasma membrane (PM) impaired DAG-activated cation currents and, upon BCR stimulation, the sustained translocation to the PM of protein kinase Cbeta (PKCbeta) that activated extracellular signal-regulated kinase (ERK). Notably, TRPC3 showed direct association with PKCbeta that maintained localization of PKCbeta at the PM. Thus, TRPC3 functions as both a Ca(2+)-permeable channel and a protein scaffold at the PM for downstream PKCbeta activation in B cells.
Numaga
Takuro
T
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
Nishida
Motohiro
M
Kiyonaka
Shigeki
S
Kato
Kenta
K
Katano
Masahiro
M
Mori
Emiko
E
Kurosaki
Tomohiro
T
Inoue
Ryuji
R
Hikida
Masaki
M
Putney
James W
JW
Mori
Yasuo
Y
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D002645:Chickens; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D015640:Ion Channel Gating; D051379:Mice; D008954:Models, Biological; D050778:NFATC Transcription Factors / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D021381:Protein Transport; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D050052:TRPC Cation Channels / Q000378:metabolism*
C011439:1,2-diacylglycerol; D015220:Calcium Channels; D004075:Diglycerides; D050778:NFATC Transcription Factors; D011947:Receptors, Antigen, B-Cell; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D048049:Extracellular Signal-Regulated MAP Kinases