Nesprin interchain associations control nuclear size.

Lu, W.; Schneider, M.; Neumann, S.; Jaeger, V-M.; Taranum, S.; Munck, M.; Cartwright, S.; Richardson, C.; Carthew, J.; Noh, K.; Goldberg, M.; Noegel, A.; Karakesisoglou, I.

Abstract

Nesprins-1/-2/-3/-4 are nuclear envelope proteins, which connect nuclei to the cytoskeleton. The largest nesprin-1/-2 isoforms (termed giant) tether F-actin through their N-terminal actin binding domain (ABD). Nesprin-3, however, lacks an ABD and associates instead to plectin, which binds intermediate filaments. Nesprins are integrated into the outer nuclear membrane via their C-terminal KASH-domain. Here, we show that nesprin-1/-2 ABDs physically and functionally interact with nesprin-3. Thus, both ends of nesprin-1/-2 giant are integrated at the nuclear surface: via the C-terminal KASH-domain and the N-terminal ABD-nesprin-3 association. Interestingly, nesprin-2 ABD or KASH-domain overexpression leads to increased nuclear areas. Conversely, nesprin-2 mini (contains the ABD and KASH-domain but lacks the massive nesprin-2 giant rod segment) expression yields smaller nuclei. Nuclear shrinkage is further enhanced upon nesprin-3 co-expression or microfilament depolymerization. Our findings suggest that multivariate intermolecular nesprin interactions with the cytoskeleton form a lattice-like filamentous network covering the outer nuclear membrane, which determines nuclear size.

Citation

Lu, W., Schneider, M., Neumann, S., Jaeger, V., Taranum, S., Munck, M., …Karakesisoglou, I. (2012). Nesprin interchain associations control nuclear size. Cellular and Molecular Life Sciences, 69(20), 3493-3509. https://doi.org/10.1007/s00018-012-1034-1

• Journal Article Type: Article
• Publication Date: 2012-10
• Deposit Date: May 14, 2012
• Journal: Cellular and Molecular Life Sciences
• Print ISSN: 1420-682X
• Electronic ISSN: 1420-9071
• Publisher: Springer
• Peer Reviewed: Peer Reviewed
• Volume: 69
• Issue: 20
• Pages: 3493-3509
• DOI: https://doi.org/10.1007/s00018-012-1034-1
• Keywords: Actin binding domain, Cytoskeleton, KASH-domain, LINC complex, Nesprin, Nuclear envelope, Nuclear shape, SUN-domain
• Public URL: https://durham-repository.worktribe.com/output/1506407