Importin-β negatively regulates multiple aspects of mitosis including RANGAP1 recruitment to kinetochores

Emanuele Roscioli, Laura Di Francesco, Alessio Bolognesi, Maria Giubettini, Serena Orlando, Amnon Harel, Maria Eugenia Schininà, Patrizia Lavia

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Importin-β is the main vector for interphase nuclear protein import and plays roles after nuclear envelope breakdown. Here we show that importin-β regulates multiple aspects of mitosis via distinct domains that interact with different classes of proteins in human cells. The C-terminal region (which binds importin-α) inhibits mitotic spindle pole formation. The central region (harboring nucleoporin-binding sites) regulates microtubule dynamic functions and interaction with kinetochores. Importin-β interacts through this region with NUP358/RANBP2, which in turn binds SUMO-conjugated RANGAP1 in nuclear pores. We show that this interaction continues after nuclear pore disassembly. Overexpression of importin-β, or of the nucleoporin-binding region, inhibited RANGAP1 recruitment to mitotic kinetochores, an event that is known to require microtubule attachment and the exportin CRM1. Co-expressing either importin-β-interacting RANBP2 fragments, or CRM1, restored RANGAP1 to kinetochores and rescued importin-β-dependent mitotic dynamic defects. These results reveal previously unrecognized importin-β functions at kinetochores exerted via RANBP2 and opposed by CRM1.

Original languageEnglish
Pages (from-to)435-450
Number of pages16
JournalJournal of Cell Biology
Issue number4
StatePublished - 20 Feb 2012
Externally publishedYes


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