期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-29725-3
关键词
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资金
- National Institutes of Health (NIH) [AI097302, AI125997, TR002873]
- NIH [GM45374, NS057499, EY026817, TR002916, AG055357]
- Alfonso Martin Escudero Foundation
- NYU (Bernard Levine postdoctoral fellowship)
- Deutsche Akademie der Naturforscher Leopoldina
- T32 training program in Immunology and Inflammation [AI100853]
- Cancer Center Support Grant NIH [P30-CA008748]
- Irma T. Hirsch career development grant
The regulatory beta subunit of voltage-gated calcium channels regulates T cell function despite no evidence that these channels were functional within T cells during activation.
TCR stimulation triggers Ca2+ signals that are critical for T cell function and immunity. Several pore-forming alpha and auxiliary beta 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 Ca-V beta 1, 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 alpha 1 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 beta 1 regulates T cell function, these effects are independent of VGCC channel activity. The function of voltage-gated calcium channels in T cells is not well understood and controversial. Here the authors report that a regulatory beta subunit of voltage-gated calcium channels regulates T cell function despite no evidence that these channels were functional within T cells during activation.
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