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Published online September 8, 2008
doi:10.1083/jcb.200805140
The Journal of Cell Biology, Vol. 182, No. 5, 911-924
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Anderson et al.
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Article

Reshaping of the endoplasmic reticulum limits the rate for nuclear envelope formation



Daniel J. Anderson and Martin W. Hetzer

Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037

Correspondence to Martin W. Hetzer: hetzer{at}salk.edu

During mitosis in metazoans, segregated chromosomes become enclosed by the nuclear envelope (NE), a double membrane that is continuous with the endoplasmic reticulum (ER). Recent in vitro data suggest that NE formation occurs by chromatin-mediated reorganization of the tubular ER; however, the basic principles of such a membrane-reshaping process remain uncharacterized. Here, we present a quantitative analysis of nuclear membrane assembly in mammalian cells using time-lapse microscopy. From the initial recruitment of ER tubules to chromatin, the formation of a membrane-enclosed, transport-competent nucleus occurs within ~12 min. Overexpression of the ER tubule-forming proteins reticulon 3, reticulon 4, and DP1 inhibits NE formation and nuclear expansion, whereas their knockdown accelerates nuclear assembly. This suggests that the transition from membrane tubules to sheets is rate-limiting for nuclear assembly. Our results provide evidence that ER-shaping proteins are directly involved in the reconstruction of the nuclear compartment and that morphological restructuring of the ER is the principal mechanism of NE formation in vivo.

Abbreviations used in this paper: NE, nuclear envelope; NPC, nuclear pore complex; Rtn3 and 4, reticulon 3 and 4, respectively.

© 2008 Anderson and Hetzer This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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