Cutting Edge: Tubulin α Functions as an Adaptor in NFAT–Importin β Interaction

Abstract

Upon T cell stimulation, NFAT is dephosphorylated by calcineurin, leading to nuclear translocation via NFAT–importin β interaction. Whereas the process of NFAT dephosphorylation has been well researched, the molecular mechanism of NFAT–importin β interaction remains unknown. In contrast to NF-κB and STAT, no importin α family members have been reported as adaptor proteins for NFAT. Our study shows that tubulin α, but not tubulin β, binds to the N-terminal region of NFAT containing the regulatory and Rel homology domains. Importin β interacts with the NFAT–tubulin α complex rather than NFAT or tubulin α alone, resulting in cotranslocation of NFAT and tubulin α into the nucleus. Furthermore, the interaction is suppressed by acetate-induced tubulin α acetylation at lysine 40. In conclusion, tubulin α functions as an adaptor in NFAT–importin β interaction, and this function is regulated by acetate-induced acetylation.