Molecular mechanisms underlying nucleocytoplasmic shuttling of actinin-4.
In addition to its well-known role as a crosslinker of actin filaments at focal-adhesion sites, actinin-4 is known to be localized to the nucleus. In this study, we reveal the molecular mechanism underlying nuclear localization of actinin-4 and its novel interactions with transcriptional regulators. We found that actinin-4 is imported into the nucleus through the nuclear pore complex in an importin-independent manner and is exported by the chromosome region maintenance-1 (CRM1)-dependent pathway. Nuclear actinin-4 levels were significantly increased in the late G2 phase of the cell cycle and were decreased in the G1 phase, suggesting that active release from the actin cytoskeleton was responsible for increased nuclear actinin-4 in late G2. Nuclear actinin-4 was found to interact with the INO80 chromatin-remodeling complex. It also directs the expression of a subset of cell-cycle-related genes and interacts with the upstream-binding factor (UBF)-dependent rRNA transcriptional machinery in the M phase. These findings provide molecular mechanisms for both nucleocytoplasmic shuttling of proteins that do not contain a nuclear-localization signal and cell-cycle-dependent gene regulation that reflects morphological changes in the cytoskeleton.
Kumeta
Masahiro
M
Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan. kumeta@lif.kyoto-u.ac.jp
Yoshimura
Shige H
SH
Harata
Masahiko
M
Takeyasu
Kunio
K
D000074183:ATPases Associated with Diverse Cellular Activities; D000185:Actinin / Q000235:genetics / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D002453:Cell Cycle / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D003001:Cloning, Molecular; D003599:Cytoskeleton; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D035463:Pol1 Transcription Initiation Complex Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction
C111453:ACTN4 protein, human; D004268:DNA-Binding Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D034741:RNA, Small Interfering; C063844:transcription factor UBF; D000185:Actinin; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C524421:INO80 protein, human