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Spindle microtubules (red) disassemble into interphase arrays (left) unless p97 is missing (right). Zheng/Elsevier

Disassembly of the mitotic spindle takes some effort, according to Kan Cao, Yixian Zheng (Johns Hopkins University, Baltimore, MD), and colleagues, who show that an ATPase and its binding partners pull apart the spindle.

The spindle is put together by assembly factors that are activated by the cyclin-dependent kinase Cdc2. The loss of Cdc2 activity at the end of mitosis has thus been the conventional explanation for spindle disassembly. "It was thought that dephosphorylation of mitotic spindle assembly factors changed microtubule dynamics directly and led to the transition into the interphase array," says Zheng. But her group finds that Cdc2 inactivation is not enough—another pathway is required to dismantle the spindle.

This pathway is organized by a complex that includes the p97 AAA-ATPase. The authors suspected p97 involvement because loss of its yeast homologue, Cdc48, causes cell cycle arrest and leaves spindles partly assembled. The group now shows that p97/Cdc48 and its adaptor proteins, Ufd1 and Npl4, take apart the spindle by removing proteins that promote its assembly.

At the end of mitosis, p97 was found to bind to XMAP215 and TPX2—two frog spindle assembly factors—and the spindle-associated kinase, Plx1. The binding prevented much of XMAP215 and TPX2 from accumulating on microtubules. In yeast cells, Cdc48 targeted similar assembly factors for degradation by the proteasome. Without p97/Cdc48 ATPase activity, yeast cells or frog oocytes that had interphase levels of Cdc2 and cyclin B were unable to dismantle mitotic spindles. Microtubules remained dynamic rather than switching to the stable growth needed for interphase array formation.

ATPases related to p97/Cdc48 are chaperones involved in protein unfolding. The p97/Cdc48 complex, however, probably uses its ATPase activity to extract proteins from the spindle and target them for degradation, as it is known to do to membrane-bound proteins at the ER.

Reference:

Cao, K., et al. 2003. Cell. 115:355–367.[CrossRef][Medline]

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article PDF (Full Text) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                      What's this?