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

Luke, Y.; Zaim, H.; Karakesisoglou, I.; Jaeger, V.M.; Sellin, L.; Lu, W.; Schneider, M.; Neumann, S.; Beijer, A.; Munck, M.; Padmakumar, V.C.; Gloy, J.; Walz, G.; Noegel, A.A.


Y. Luke

H. Zaim

V.M. Jaeger

L. Sellin

W. Lu

M. Schneider

S. Neumann

A. Beijer

M. Munck

V.C. Padmakumar

J. Gloy

G. Walz

A.A. Noegel


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-2DeltaABD). 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.


Luke, Y., Zaim, H., Karakesisoglou, I., Jaeger, V., Sellin, L., Lu, W., …Noegel, A. (2008). Nesprin-2 Giant (NUANCE) maintains nuclear envelope architecture and composition in skin. Journal of Cell Science, 121(11), 1887-1898.

Journal Article Type Article
Publication Date 2008
Journal Journal of Cell Science
Print ISSN 0021-9533
Electronic ISSN 1477-9137
Publisher The Company of Biologists
Volume 121
Issue 11
Pages 1887-1898