Critical role for the beta regulatory subunits of Cav channels in T lymphocyte function.
Calcium ion is a universal signaling intermediate, which is known to control various biological processes. In excitable cells, voltage-gated calcium channels (Cav) are the major route of calcium entry and regulate multiple functions such as contraction, neurotransmitter release, and gene transcription. Here we show that T lymphocytes, which are nonexcitable cells, express both regulatory beta and pore-forming Cav1 alpha1 subunits of Cav channels, and we provide genetic evidence for a critical role of the Cav beta3 and Cav beta4 regulatory subunits in T lymphocyte function. Cav beta-deficient T lymphocytes fail to acquire normal functions, and they display impairment in the T cell receptor-mediated calcium response, nuclear factor of activated T cells activation, and cytokine production. In addition, unlike in excitable cells, our data suggest a minimal physiological role for depolarization in Cav channel opening in T cells. T cell receptor stimulation induces only a small depolarization of T cells, and artificial depolarization of T cells using KCl does not lead to calcium entry. These observations suggest that the Cav channels expressed by T cells have adopted novel regulation/gating mechanisms.
Badou
Abdallah
A
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Jha
Mithilesh Kumar
MK
Matza
Didi
D
Mehal
Wajahat Z
WZ
Freichel
Marc
M
Flockerzi
Veit
V
Flavell
Richard A
RA
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*
D020746:Calcium Channels, L-Type; D016207:Cytokines; D005456:Fluorescent Dyes; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell; D002118:Calcium