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Durham University

Department of Biosciences

Academic Staff

Publication details for Dr Akis (Iakowos) Karakesisoglou

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. (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.

Author(s) from Durham

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.