Transportin regulates major mitotic assembly events: from spindle to nuclear pore assembly

Corine K. Lau, Valerie A. Delmar, Rene C. Chan, Quang Phung, Cyril Bernis, Boris Fichtman, Beth A. Rasala, Douglass J. Forbes

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Mitosis in higher eukaryotes is marked by the sequential assembly of two massive structures: the mitotic spindle and the nucleus. Nuclear assembly itself requires the precise formation of both nuclear membranes and nuclear pore complexes. Previously, importin alpha/beta and RanGTP were shown to act as dueling regulators to ensure that these assembly processes occur only in the vicinity of the mitotic chromosomes. We now find that the distantly related karyopherin, transportin, negatively regulates nuclear envelope fusion and nuclear pore assembly in Xenopus egg extracts. We show that transportin - and importin beta - initiate their regulation as early as the first known step of nuclear pore assembly: recruitment of the critical pore-targeting nucleoporin ELYS/MEL-28 to chromatin. Indeed, each karyopherin can interact directly with ELYS. We further define the nucleoporin subunit targets for transportin and importin beta and find them to be largely the same: ELYS, the Nup107/160 complex, Nup53, and the FG nucleoporins. Equally importantly, we find that transportin negatively regulates mitotic spindle assembly. These negative regulatory events are counteracted by RanGTP. We conclude that the interplay of the two negative regulators, transportin and importin beta, along with the positive regulator RanGTP, allows precise choreography of multiple cell cycle assembly events.

Original languageEnglish
Pages (from-to)4043-4058
Number of pages16
JournalMolecular Biology of the Cell
Volume20
Issue number18
DOIs
StatePublished - 15 Sep 2009
Externally publishedYes

Funding

FundersFunder number
National Institute of General Medical SciencesR01GM033279

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