Defective survival of naive CD8+ T lymphocytes in the absence of the beta3 regulatory subunit of voltage-gated calcium channels.
The survival of T lymphocytes requires sustained, Ca(2+) influx-dependent gene expression. The molecular mechanism that governs sustained Ca(2+) influx in naive T lymphocytes is unknown. Here we report an essential role for the beta3 regulatory subunit of voltage-gated calcium (Ca(v)) channels in the maintenance of naive CD8(+) T cells. Deficiency in beta3 resulted in a profound survival defect of CD8(+) T cells. This defect correlated with depletion of the pore-forming subunit Ca(v)1.4 and attenuation of T cell antigen receptor (TCR)-mediated global Ca(2+) entry in CD8(+) T cells. Ca(v)1.4 and beta3 associated with T cell signaling machinery and Ca(v)1.4 localized in lipid rafts. Our data demonstrate a mechanism by which Ca(2+) entry is controlled by a Ca(v)1.4-beta3 channel complex in T cells.
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Mithilesh K
MK
Jha
Abdallah
A
Badou
Marcel
M
Meissner
John E
JE
McRory
Marc
M
Freichel
Veit
V
Flockerzi
Richard A
RA
Flavell
D000818:Animals; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D015220:Calcium Channels / Q000172:deficiency* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020746:Calcium Channels, L-Type; D020013:Calcium Signaling; D002470:Cell Survival; D005786:Gene Expression Regulation; D006706:Homeostasis; D007113:Immunity, Innate; D051379:Mice; D018345:Mice, Knockout; D019014:fas Receptor / Q000378:metabolism
C480684:Cacna1f protein, mouse; C510225:Cacnb3 protein, mouse; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D019014:fas Receptor