spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 13 May 2008
doi: 10.1242/jcs.019075

Journal of Cell Science 121, 1887-1898 (2008)
Published by The Company of Biologists 2008
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow All Versions of this Article:
jcs.019075v1
121/11/1887    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Lüke, Y.
Right arrow Articles by Noegel, A. A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lüke, Y.
Right arrow Articles by Noegel, A. A.

Research Article

Nesprin-2 Giant (NUANCE) maintains nuclear envelope architecture and composition in skin

Yvonne Lüke1,*, Hafida Zaim1,*, Iakowos Karakesisoglou1,2,*, Verena M. Jaeger1, Lorenz Sellin3, Wenshu Lu1, Maria Schneider1, Sascha Neumann1,4, Asa Beijer1, Martina Munck1,4, V. C. Padmakumar1,4, Joachim Gloy3, Gerd Walz3 and Angelika A. Noegel1,4,{ddagger}

1 Center for Biochemistry, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 Cologne, Germany
2 Department of Biological Sciences, The School of Biological and Biomedical Sciences, The University of Durham, Durham DH1 3LE, UK
3 Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany
4 Center for Molecular Medicine Cologne (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany

{ddagger} Author for correspondence (e-mail: Noegel{at}uni-koeln.de)

Accepted 20 March 2008

Giant isoforms, encoded by Nesprin-1 (Syne1) and Nesprin-2 (Syne2), are multifunctional actin-binding and nuclear-envelope-associated proteins belonging to the spectrin superfamily. Here, we investigate the function of Nesprin-2 Giant (NUANCE) in skin by generating mice lacking the actin-binding domain of Nesprin-2 (Nesprin-2{Delta}ABD). This loss results in a slight but significant thickening of the epidermis, which is a consequence of the increased epithelial nuclear size. Nonetheless, epidermal proliferation and differentiation appear normal in the knockout epidermis. Surprisingly, Nesprin-2 C-terminal-isoform expression and nuclear envelope localization were affected in certain tissues. Nuclei of primary dermal knockout fibroblasts and keratinocytes were heavily misshapen, displaying a striking similarity to nuclear deformations characteristic of laminopathies. Furthermore, emerin, the protein involved in the X-linked form of Emery-Dreifuss muscular dystrophy (EDMD), was unevenly distributed along the nuclear envelope in mutant fibroblasts, often forming aggregates in the deformed nuclear envelope areas. Thus, Nesprin-2 is an important scaffold protein implicated in the maintenance of nuclear envelope architecture. Aged knockout fibroblasts readily generated, by alternative splicing and alternative translation initiation, aberrant Nesprin-2 Giant isoforms that lacked an ABD but that were sufficient to restore nuclear shape and emerin localization; this suggests that other regions of Nesprin-2 Giant, potentially including its spectrin repeats, are crucial for these functions.

Key words: KASH-domain, Mouse knockout, Laminopathies, Nuclear shape, Cell migration, Cell polarity






© The Company of Biologists Ltd 2008