Year: 2021
Type: article
Abstract: Sustained activation of the Ca 2+ -release-activated Ca 2+ (CRAC) channel is pivotal for effector T cell responses. The mechanisms underlying this sustainability remain poorly understood. We find that plasma membrane localization of ORAI1, the pore subunit of CRAC channels, is limited in effector T cells, with a significant fraction trapped in intracellular vesicles. From a targeted screen, we identify an essential component of ORAI1 + vesicles, naked cuticle homolog 2 (NKD2). Mechanistically, NKD2, an adaptor molecule activated by signaling pathways downstream of T cell receptors, orchestrates trafficking and insertion of ORAI1 + vesicles to the plasma membrane. Together, our findings suggest that T cell receptor (TCR)-stimulation-dependent insertion of ORAI1 into the plasma membrane is essential for sustained Ca 2+ signaling and cytokine production in T cells.
Source: Cell Reports
Authors: Beibei Wu, Jin Seok Woo, Pamela Vila, Marcus Jew, Jennifer Leung, Zuoming Sun, Sonal Srikanth, Yousang Gwack
Language: English
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: National Institutes of Health, University of California, Los Angeles, Center for AIDS Research, University of Washington, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, UCLA AIDS Institute
Awards: G1685810784, Regulation of the STING pathway under sterile conditions, Distinct functions of Orai1 and Orai2 in naive and effector helper T cells, G2524606428, G2614396188, Function of TCF-1 in antagonizing malignancy, Development of an animal model of severe neutrophilic asthma, Role of Orai1 trafficking in local effector T cell responses, Mechanism underlying regulation of Ca2+ signaling in local effector T cells, Distinctive role of ORAI3 channels in the effector T cell response, Novel lymphocyte-specific Rab GTPase in T cell differentiation, G7710859931, UCLA Center for AIDS Research (CFAR), G9000006425, Cbfb in RORgt-regulated T cell function, Cancer Center Support Grant
OpenAlex ID: W3194686947