Roles of Ca(v) channels and AHNAK1 in T cells: the beauty and the beast.
T lymphocytes require Ca2+ entry though the plasma membrane for their activation and function. Recently, several routes for Ca2+ entry through the T-cell plasma membrane after activation have been described. These include calcium release-activated channels (CRAC), transient receptor potential (TRP) channels, and inositol-1,4,5-trisphosphate receptors (IP3Rs). Herein we review the emergence of a fourth new route for Ca2+ entry, composed of Ca(v) channels (also known as L-type voltage-gated calcium channels) and the scaffold protein AHNAK1 (AHNAK/desmoyokin). Both helper (CD4+) and killer (CD8+) T cells express high levels of Ca(v)1 alpha1 subunits (alpha1S, alpha1C, alpha1D, and alpha1F) and AHNAK1 after their differentiation and require these molecules for Ca2+ entry during an immune response. In this article, we describe the observations and open questions that ultimately suggest the involvement of multiple consecutive routes for Ca2+ entry into lymphocytes, one of which may be mediated by Ca(v) channels and AHNAK1.
Matza
Didi
D
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Flavell
Richard A
RA
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002454:Cell Differentiation; D003896:Desmosomes / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D008565:Membrane Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D015220:Calcium Channels; D008565:Membrane Proteins