Cavβ1 regulates T cell expansion and apoptosis independently of voltage-gated Ca2+ channel function
Serap Erdogmus, Axel R. Concepcion, Megumi Yamashita, Ikjot Sidhu, Anthony Tao, Wenyi Li, Pedro P. Rocha, Bonnie Huang, Ralph Garippa, Bo Ram Lee, Amy Lee, Johannes Hell, Richard S. Lewis, Murali Prakriya, Stefan Feske
Abstract
Abstract TCR stimulation triggers Ca 2+ signals that are critical for T cell function and immunity. Several pore-forming α and auxiliary β subunits of voltage-gated Ca 2+ channels (VGCC) were reported in T cells, but their mechanism of activation remains elusive and their contribution to Ca 2+ signaling in T cells is controversial. We here identify Ca V β1, encoded by Cacnb1 , as a regulator of T cell function. Cacnb1 deletion enhances apoptosis and impairs the clonal expansion of T cells after lymphocytic choriomeningitis virus (LCMV) infection. By contrast, Cacnb1 is dispensable for T cell proliferation, cytokine production and Ca 2+ signaling. Using patch clamp electrophysiology and Ca 2+ recordings, we are unable to detect voltage-gated Ca 2+ currents or Ca 2+ influx in human and mouse T cells upon depolarization with or without prior TCR stimulation. mRNAs of several VGCC α1 subunits are detectable in human (Ca V 3.3, Ca V 3.2) and mouse (Ca V 2.1) T cells, but they lack transcription of many 5’ exons, likely resulting in N-terminally truncated and non-functional proteins. Our findings demonstrate that although Ca V β1 regulates T cell function, these effects are independent of VGCC channel activity.