Essential roles for Cavβ2 and Cav1 channels in thymocyte development and T cell homeostasis

• Verfasst von: Jha, Archana [VerfasserIn]
• Verfasst von: Freichel, Marc [VerfasserIn]
• Titel: Essential roles for Cavβ2 and Cav1 channels in thymocyte development and T cell homeostasis
• Verf.angabe: Archana Jha, Ashish K. Singh, Petra Weissgerber, Marc Freichel, Veit Flockerzi, Richard A. Flavell, and Mithilesh K. Jha
• E-Jahr: 2015
• Jahr: 20 Oct 2015
• Umfang: ? S.
• Fussnoten: Im Titel wird beta als griechischer Buchstabe dargestellt ; Im Titel ist der Buchstabe v tiefgestellt ; Gesehen am 09.06.2020
• Titel Quelle: Enthalten in: Science signaling
• Ort Quelle: Washington, DC [u.a.] : Assoc., 2008
• Jahr Quelle: 2015
• Band/Heft Quelle: 8(2015,399) Artikel-Nummer ra103, ? Seiten
• ISSN Quelle: 1937-9145
• DOI: doi:10.1126/scisignal.aac7538
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1700235338

Abstract

Channeling calcium for T cell development - Ca2+ signaling in response to stimulation of the T cell receptor (TCR) is critical to the activation of transcription factors, such as nuclear factor of activated T cells (NFAT), and the development of T cells in the thymus. Jha et al. found that mice with a T cell-specific deficiency in the β2 regulatory subunit of voltage-gated calcium (Cav) channels had fewer thymocytes and peripheral T cells than did control mice. Loss of the β2 subunit resulted in decreased Ca2+ influx in thymocytes in response to TCR stimulation, defective NFAT responses, and decreased thymocyte proliferation. Together, these data suggest that Cav channels contribute to the Ca2+ influx that is required for T cell development. - Calcium ions (Ca2+) are important in numerous signal transduction processes, including the development and differentiation of T cells in the thymus. We report that thymocytes have multiple types of pore-forming α subunits and regulatory β subunits that constitute voltage-gated Ca2+ (Cav) channels. In mice, T cell-specific deletion of the gene encoding the β2 regulatory subunit of Cav channels (Cacnb2) reduced the abundances of the channels Cav1.2 and Cav1.3 (both of which contain pore-forming α1 subunits) and impaired T cell development, which led to a substantial decrease in the numbers of thymocytes and peripheral T cells. Similar to the effect of Cacnb2 deficiency, pharmacological blockade of pore-forming Cav1α subunits reduced the sustained Ca2+ influx in thymocytes upon stimulation of the T cell receptor, decreased the abundance of the transcription factor NFATc3, inhibited the proliferation of thymocytes in vitro, and led to lymphopenia in mice. Together, our data suggest that Cav1 channels are conduits for the sustained Ca2+ influx that is required for the development of T cells. - Disruption of voltage-gated calcium channels in thymocytes inhibits T cell development in mice. - Disruption of voltage-gated calcium channels in thymocytes inhibits T cell development in mice.