title: The Ca(v)1.4 calcium channel is a critical regulator of T cell receptor signaling and naive T cell homeostasis.
abstract: The transport of calcium ions (Ca(2+)) to the cytosol is essential for immunoreceptor signaling, regulating lymphocyte differentiation, activation, and effector function. Increases in cytosolic-free Ca(2+) concentrations are thought to be mediated through two interconnected and complementary mechanisms: the release of endoplasmic reticulum Ca(2+) "stores" and "store-operated" Ca(2+) entry via plasma membrane channels. However, the identity of molecular components conducting Ca(2+) currents within developing and mature T cells is unclear. Here, we have demonstrated that the L-type "voltage-dependent" Ca(2+) channel Ca(V)1.4 plays a cell-intrinsic role in the function, development, and survival of naive T cells. Plasma membrane Ca(V)1.4 was found to be essential for modulation of intracellular Ca(2+) stores and T cell receptor (TCR)-induced rises in cytosolic-free Ca(2+), impacting activation of Ras-extracellular signal-regulated kinase (ERK) and nuclear factor of activated T cells (NFAT) pathways. Collectively, these studies revealed that Ca(V)1.4 functions in controlling naive T cell homeostasis and antigen-driven T cell immune responses.
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Kyla
authors.initials: K
authors.lastname: Omilusik
authors.forename: John J
authors.initials: JJ
authors.lastname: Priatel
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Chen
authors.forename: Yiwen Teresa
authors.initials: YT
authors.lastname: Wang
authors.forename: Hongjian
authors.initials: H
authors.lastname: Xu
authors.forename: Kyung Bok
authors.initials: KB
authors.lastname: Choi
authors.forename: Rayshad
authors.initials: R
authors.lastname: Gopaul
authors.forename: Adam
authors.initials: A
authors.lastname: McIntyre-Smith
authors.forename: Hung-Sia
authors.initials: HS
authors.lastname: Teh
authors.forename: Rusung
authors.initials: R
authors.lastname: Tan
authors.forename: N Torben
authors.initials: NT
authors.lastname: Bech-Hansen
authors.forename: Douglas
authors.initials: D
authors.lastname: Waterfield
authors.forename: David
authors.initials: D
authors.lastname: Fedida
authors.forename: Simon V
authors.initials: SV
authors.lastname: Hunt
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: Jefferies
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D049109:Cell Proliferation; D002478:Cells, Cultured; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018631:ras Proteins / Q000378:metabolism
chemical_list: C480684:Cacna1f protein, mouse; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; D018631:ras Proteins; D002118:Calcium