Multifaceted control of T cell differentiation by STIM1.

In T cells, stromal interaction molecule (STIM) and Orai are dispensable for conventional T cell development, but critical for activation and differentiation. This review focuses on novel STIM-dependent mechanisms for control of Ca signals during T cell activation and its impact on mitochondrial function and transcriptional activation for control of T cell differentiation and function. We highlight areas that require further work including the roles of plasma membrane Ca ATPase (PMCA) and partner of STIM1 (POST) in controlling Orai function. A major knowledge gap also exists regarding the independence of T cell development from STIM and Orai, despite compelling evidence that it requires Ca signals. Resolving these and other outstanding questions ensures that the field will remain active for many years to come.

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