Cavβ1 regulates T cell expansion and apoptosis independently of voltage-gated Ca2+ channel function

Serap Erdogmus, Axel R. Concepcion, Megumi Yamashita, Ikjot Sidhu, Anthony Y. Tao, Wenyi Li, Pedro P. Rocha, Bonnie Huang, Ralph Garippa, Boram Lee, Amy Lee, Johannes W. Hell, Richard S. Lewis, Murali Prakriya, Stefan Feske*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

TCR stimulation triggers Ca2+ signals that are critical for T cell function and immunity. Several pore-forming α and auxiliary β subunits of voltage-gated Ca2+ channels (VGCC) were reported in T cells, but their mechanism of activation remains elusive and their contribution to Ca2+ signaling in T cells is controversial. We here identify CaVβ1, 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 Ca2+ signaling. Using patch clamp electrophysiology and Ca2+ recordings, we are unable to detect voltage-gated Ca2+ currents or Ca2+ 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 (CaV3.3, CaV3.2) and mouse (CaV2.1) 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 CaVβ1 regulates T cell function, these effects are independent of VGCC channel activity.

Original languageEnglish (US)
Article number2033
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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