Importin α transports CaMKIV to the nucleus without utilizing importin β

Abstract

Ca(2+)/calmodulin-dependent protein kinase type IV (CaMKIV) plays an essential role in the transcriptional activation of cAMP response element-binding protein-mediated signaling pathways. Although CaMKIV is localized predominantly in the nucleus, the molecular mechanism of the nuclear import of CaMKIV has not been elucidated. We report here that importin α is able to carry CaMKIV into the nucleus without the need for importin β or any other soluble proteins in digitonin-permeabilized cells. An importin β binding-deficient mutant (ΔIBB) of importin α also carried CaMKIV into the nucleus, which strongly suggests that CaMKIV is transported in an importin β-independent manner. While CaMKIV directly interacted with the C-terminal region of importin α, the CaMKIV/importin α complex did not form a ternary complex with importin β, which explains the nonrequirement of importin β for the nuclear transport of CaMKIV. The cytoplasmic microinjection of importin α-ΔIBB enhanced the rate of nuclear translocation of CaMKIV in vivo. This is the first report to demonstrate definitely that mammalian importin α solely carries a cargo protein into the nucleus without utilizing the classical importin β-dependent transport system