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J. Biol. Chem., Vol. 280, Issue 50, 41628-41635, December 16, 2005

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Endocytosis Resumes during Late Mitosis and Is Required for Cytokinesis^*

Jill Kuglin Schweitzer¶1, Erin E. Burke, Holly V. Goodson¶, and Crislyn D'Souza-Schorey¶2

From the Departments of Biological Sciences, Chemistry and Biochemistry, and the ^¶Walther Cancer Center, University of Notre Dame, Notre Dame, Indiana 46556-0369

Recent work has underscored the importance of membrane trafficking events during cytokinesis. For example, targeted membrane secretion occurs at the cleavage furrow in animal cells, and proteins that regulate endocytosis also influence the process of cytokinesis. Nonetheless, the prevailing dogma is that endosomal membrane trafficking ceases during mitosis and resumes after cell division is complete. In this study, we have characterized endocytic membrane trafficking events that occur during mammalian cell cytokinesis. We have found that, although endocytosis ceases during the early stages of mitosis, it resumes during late mitosis in a temporally and spatially regulated pattern as cells progress from anaphase to cytokinesis. Using fixed and live cell imaging, we have found that, during cleavage furrow ingression, vesicles are internalized from the polar region and subsequently trafficked to the midbody area during later stages of cytokinesis. In addition, we have demonstrated that cytokinesis is inhibited when clathrin-mediated endocytosis is blocked using a series of dominant negative mutants. In contrast to previous thought, we conclude that endocytosis resumes during the later stages of mitosis, before cytokinesis is completed. Furthermore, based on our findings, we propose that the proper regulation of endosomal membrane traffic is necessary for the successful completion of cytokinesis.

Received for publication, April 25, 2005 , and in revised form, September 26, 2005.

^* This work was supported in part by grants from the United States Department of Defense and the American Cancer Society (RSG 03-023-01-CSM) (to C. D-S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1-7, of which supplemental Figs. 3-6 consist of both still images and videos.

¹ Recipient of a Special Fellow Career Development Award from The Leukemia and Lymphoma Society.

² To whom correspondence should be addressed: Dept. of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556-0369. Tel.: 574-631-3735; Fax: 574-631-7413; E-mail: D'Souza-Schorey.1{at}nd.edu.

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