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Critical role for the β regulatory subunits of Cav channels in T lymphocyte function

2006; National Academy of Sciences; Volume: 103; Issue: 42 Linguagem: Inglês

10.1073/pnas.0607262103

1091-6490

Abdallah Badou, Mithilesh Kumar Jha, Didi Matza, Wajahat Z. Mehal, Marc Freichel, Veit Flockerzi, Richard A. Flavell,

Neuroscience and Neuropharmacology Research

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 β and pore-forming Cav1 α1 subunits of Cav channels, and we provide genetic evidence for a critical role of the Cav β3 and Cav β4 regulatory subunits in T lymphocyte function. Cav β-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.