Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration

Cyril Bernis, Beth Swift-Taylor, Matthew Nord, Sarah Carmona, Yuh Min Chook, Douglass J. Forbes

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


The nuclear import receptors importin ß and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin ß is known to act by repressing assembly factors in regions distant from chromatin, whereas RanGTP produced on chromatin frees factors from importin ß for localized assembly. The mechanism of transportin regulation was unknown. Diametrically opposed models for transportin action are as follows: 1) indirect action by RanGTP sequestration, thus down-regulating release of assembly factors from importin ß, and 2) direct action by transportin binding and inhibiting assembly factors. Experiments in Xenopus assembly extracts with M9M, a superaffinity nuclear localization sequence that displaces cargoes bound by transportin, or TLB, a mutant transportin that can bind cargo and RanGTP simultaneously, support direct inhibition. Consistently, simple addition of M9M to mitotic cytosol induces microtubule aster assembly. ELYS and the nucleoporin 107-160 complex, components of mitotic kinetochores and nuclear pores, are blocked from binding to kinetochores in vitro by transportin, a block reversible by M9M. In vivo, 30% of M9M-transfected cells have spindle/cytokinesis defects. We conclude that the cell contains importin ß and transportin "global positioning system"or "GPS" pathways that are mechanistically parallel.

Original languageEnglish (US)
Pages (from-to)992-1009
Number of pages18
JournalMolecular biology of the cell
Issue number7
StatePublished - Apr 1 2014

ASJC Scopus subject areas

  • Medicine(all)


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