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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.

Authors

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



Abstract

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.

Citation

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. https://doi.org/10.1242/jcs.019075

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
DOI https://doi.org/10.1242/jcs.019075