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Published online 27 December 2005. doi:10.1083/jcb.200509124
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 1, 41-53
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Article

Coupling of the nucleus and cytoplasm

: role of the LINC complex



Melissa Crisp1, Qian Liu1, Kyle Roux1, J.B. Rattner4, Catherine Shanahan3, Brian Burke1, Phillip D. Stahl2, and Didier Hodzic2

1 Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610
2 Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110
3 Division of Cardiovascular Medicine, Addenbrooke's Centre for Clinical Investigation, Cambridge CB2 2QQ, UK
4 Department of Cell Biology and Anatomy, University of Calgary, Calgary AB T2N 4N1, Canada

Correspondence to Didier Hodzic: dhodzic{at}cellbiology.wustl.edu; or Brian Burke: bburke{at}anatomy.med.ufl.edu

The nuclear envelope defines the barrier between the nucleus and cytoplasm and features inner and outer membranes separated by a perinuclear space (PNS). The inner nuclear membrane contains specific integral proteins that include Sun1 and Sun2. Although the outer nuclear membrane (ONM) is continuous with the endoplasmic reticulum, it is nevertheless enriched in several integral membrane proteins, including nesprin 2 Giant (nesp2G), an 800-kD protein featuring an NH2-terminal actin-binding domain. A recent study (Padmakumar, V.C., T. Libotte, W. Lu, H. Zaim, S. Abraham, A.A. Noegel, J. Gotzmann, R. Foisner, and I. Karakesisoglou. 2005. J. Cell Sci. 118:3419–3430) has shown that localization of nesp2G to the ONM is dependent upon an interaction with Sun1. In this study, we confirm and extend these results by demonstrating that both Sun1 and Sun2 contribute to nesp2G localization. Codepletion of both of these proteins in HeLa cells leads to the loss of ONM-associated nesp2G, as does overexpression of the Sun1 lumenal domain. Both treatments result in the expansion of the PNS. These data, together with those of Padmakumar et al. (2005), support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS. In this way, Sun proteins and nesprins form a complex that links the nucleoskeleton and cytoskeleton (the LINC complex).

Abbreviations used in this paper: ABD, actin-binding domain; INM, inner nuclear membrane; MEF, mouse embryonic fibroblast; NE, nuclear envelope; NPC, nuclear pore complex; ONM, outer nuclear membrane; PNS, perinuclear space; RNAi, RNA interference; siRNA, short inhibitory RNA.


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