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Roles of Cav channels and AHNAK1 in T cells: the beauty and the beast

Summary:  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 Cav 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 Cav1 α1 subunits (α1S, α1C, α1D, and α1F) 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 Cav channels and AHNAK1.