Publication details for Dr Martin GoldbergLu, 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. (2012). Nesprin interchain associations control nuclear size. Cellular and Molecular Life Sciences 69(20): 3493-3509.
- Publication type: Journal Article
- ISSN/ISBN: 1420-682X, 1420-9071
- DOI: 10.1007/s00018-012-1034-1
- Keywords: Actin binding domain, Cytoskeleton, KASH-domain, LINC complex, Nesprin, Nuclear envelope, Nuclear shape, SUN-domain
- Further publication details on publisher web site
Author(s) from Durham
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.