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 () and Stefan Feske ()
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Serap Erdogmus: Department of Pathology, NYU Grossman School of Medicine
Axel R. Concepcion: Department of Pathology, NYU Grossman School of Medicine
Megumi Yamashita: Northwestern University
Ikjot Sidhu: Department of Pathology, NYU Grossman School of Medicine
Anthony Y. Tao: Department of Pathology, NYU Grossman School of Medicine
Wenyi Li: Department of Pathology, NYU Grossman School of Medicine
Pedro P. Rocha: National Institute of Child Health and Human Development, National Institutes of Health
Bonnie Huang: National Institute of Allergy and Infectious Disease
Ralph Garippa: Memorial Sloan Kettering Cancer Center
Boram Lee: University of California
Amy Lee: University of Texas-Austin
Johannes W. Hell: University of California
Richard S. Lewis: Stanford University
Murali Prakriya: Northwestern University
Stefan Feske: Department of Pathology, NYU Grossman School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29725-3

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