A revised model of nuclear actin import: Importin 9 competes with cofilin, profilin, and RanGTP for actin binding.

ABSTRACT: While predominantly studied in cytoplasmic contexts, actin plays critical roles in the nucleus, regulating genome accessibility, transcription, and DNA repair. Cell-based studies have contributed to a widely accepted model in which the import factor importin 9 (IPO9) acts in concert with the actin filament-severing protein cofilin to transport actin into the nucleus. The classical nuclear localization signal on cofilin is thought to anchor IPO9 to cofilin-bound actin monomers, driving the formation of an import-competent tripartite actin-cofilin-IPO9 complex. Contrary to this established model of actin import, we demonstrate that IPO9 directly binds to monomeric actin with midnanomolar affinity and, rather than promoting IPO9-actin complex formation, cofilin competitively inhibits the bind

SUBMITTER: Keplinger AJ 

PROVIDER: S-EPMC12860355 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature