Nesprin interchain associations control nuclear size

Lu, W; Schneider, M; Neumann, S; Jaeger, VM; Taranum, S; Munck, M; Cartwright, S; Richardson, C; Carthew, J; Noh, K; Goldberg, M; Noegel, AA; Karakesisoglou, I

HERO ID

1450053

Reference Type

Journal Article

Year

2012

Language

English

PMID

22653047

HERO ID 1450053
In Press No
Year 2012
Title Nesprin interchain associations control nuclear size
Authors Lu, W; Schneider, M; Neumann, S; Jaeger, VM; Taranum, S; Munck, M; Cartwright, S; Richardson, C; Carthew, J; Noh, K; Goldberg, M; Noegel, AA; Karakesisoglou, I
Journal Cellular and Molecular Life Sciences (CMLS)
Volume 69
Issue 20
Page Numbers 3493-3509
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.
Doi 10.1007/s00018-012-1034-1
Pmid 22653047
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English