Lamin A/C-dependent localization of Nesprin-2, a giant scaffolder at the nuclear envelope

Libotte, T.; Zaim, H.; Abraham, S.; Padmakumar, V.C.; Schneider, M.; Lu, W.S.; Munck, M.; Hutchison, C.; Wehnert, M.; Fahrenkrog, B.; Sauder, U.; Aebi, U.; Noegel, A.A.; Karakesisoglou, I.

Abstract

The vertebrate proteins Nesprin-1 and Nesprin-2 (also referred to as Enaptin and NUANCE) together with ANC-1 of Caenorhabditis elegans and MSP-300 of Drosophila melanogaster belong to a novel family of -actinin type actin-binding proteins residing at the nuclear membrane. Using biochemical techniques, we demonstrate that Nesprin-2 binds directly to emerin and the C-terminal common region of lamin A/C. Selective disruption of the lamin A/C network in COS7 cells, using a dominant negative lamin B mutant, resulted in the redistribution of Nesprin-2. Furthermore, using lamin A/C knockout fibroblasts we show that lamin A/C is necessary for the nuclear envelope localization of Nesprin-2. In normal skin where lamin A/C is differentially expressed, strong Nesprin-2 expression was found in all epidermal layers, including the basal layer where only lamin C is present. This indicates that lamin C is sufficient for proper Nesprin-2 localization at the nuclear envelope. Expression of dominant negative Nesprin-2 constructs and knockdown studies in COS7 cells revealed that the presence of Nesprin-2 at the nuclear envelope is necessary for the proper localization of emerin. Our data imply a scaffolding function of Nesprin-2 at the nuclear membrane and suggest a potential involvement of this multi-isomeric protein in human disease.

Citation

Libotte, T., Zaim, H., Abraham, S., Padmakumar, V., Schneider, M., Lu, W., …Karakesisoglou, I. (2005). Lamin A/C-dependent localization of Nesprin-2, a giant scaffolder at the nuclear envelope. Molecular Biology of the Cell, 16(7), 3411-3424. https://doi.org/10.1091/mbc.e04-11-1009

• Journal Article Type: Article
• Publication Date: Jul 1, 2005
• Deposit Date: Oct 1, 2008
• Publicly Available Date: Oct 1, 2008
• Journal: Molecular biology of the cell
• Publisher: American Society for Cell Biology
• Peer Reviewed: Peer Reviewed
• Volume: 16
• Issue: 7
• Pages: 3411-3424
• DOI: https://doi.org/10.1091/mbc.e04-11-1009
• Public URL: https://durham-repository.worktribe.com/output/1558838