Nuclear envelope breakdown is a critical step in the cell cycle of higher eukaryotes. Although integral membrane proteins associated with the nuclear membrane have been observed to disperse into the endoplasmic reticulum at mitosis, the mechanisms involved in this reorganization remain to be fully elucidated. Here, using Xenopus extracts, we report a role for the COPI coatomer complex in nuclear envelope breakdown, implicating vesiculation as an important step. We have found that a nuclear pore protein, Nup153, plays a critical role in directing COPI to the nuclear membrane at mitosis and that this event provides feedback to other aspects of nuclear disassembly. These results provide insight into how key steps in nuclear division are orchestrated.
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We would like to thank members of the Ullman lab for helpful discussion and Meda Higa and Brian Bennion for reagents. We are grateful to Dale Shumaker and Robert Goldman for the kind of gift of anti-lamin antibodies and to Chris Rodesch for sharing his expertise in microscopy. We also thank Janet Shaw, Jerry Kaplan, and Maureen Powers for critical reading of the manuscript. This work was supported by National Institutes of Health Grant GM61275 and a Burroughs Wellcome Career Award in Biomedical Science (to K.S.U.). A.J.P. was supported by a predoctoral fellowship from the National Science Foundation. We also gratefully acknowledge support from the Huntsman Cancer Foundation. Core facilities used in this study are partially supported by National Institutes of Health grant (P30 CA42014) to the University of Utah.