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Vol. 20, Issue 18, 4043-4058, September 15, 2009

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E09-02-0152v1 20/18/4043    most recent Alert me when this article is cited Alert me if a correction is posted Services Related articles in Mol. Biol. Cell Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Lau, C. K. Articles by Forbes, D. J. PubMed PubMed Citation Articles by Lau, C. K. Articles by Forbes, D. J.

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^*,, and Douglass J. Forbes^*

*Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0347

Submitted February 23, 2009; Accepted July 22, 2009
Monitoring Editor: Susan R. Wente

InCytes from MBC

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.

These authors contributed equally to this work.

Present addresses: Department of Developmental Biology, Stanford University, Stanford, CA 94305;

The Scripps Research Institute, La Jolla, CA 92037.

Address correspondence to: Douglass J. Forbes (dforbes{at}ucsd.edu).

Abbreviations used: AL, annulate lamellae; FG, phenylalanine-glycine; GST, glutathione-S-transferase; NLS, nuclear localization signal; PY, proline-tyrosine; SAF, spindle assembly factors; Trn, transportin.

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