Tespa1 is a novel inositol 1,4,5-trisphosphate receptor binding protein in T and B lymphocytes

Tespa1 has been recently reported to be a critical molecule in T-cell development, however, the precise molecular mechanisms of Tespa1 remain elusive. Here, we demonstrate that Tespa1 shows amino-acid sequence homology to KRAS-induced actin-interacting protein (KRAP), an inositol 1,4,5-trisphosphate receptor (IP3R) binding protein, and that Tespa1 physically associates with IP3R in T and B lymphocytes. Two-consecutive phenylalanine residues (Phe185/Phe186) in Tespa1, which are conserved between Tespa1 and KRAP, are indispensable for the association between Tespa1 and IP3R. These findings suggest that Tespa1 plays critical roles in the immune system through the regulation of the IP3R.

▸ We identified Tespa1 as a novel IP3R-associated protein in lymphoid tissues. ▸ Tespa1 interacts with multiple subtypes of IP3R in T and B lymphocytes. ▸ Amino-terminal region of IP3R is sufficient for the association with Tespa1. ▸ Two consecutive phenylalanines in Tespa1 are critical for the interaction with IP3R. ▸ Tespa1 is structurally and functionally related to KRAP.