The Nesprins are the only protein family known to localise specifically to the outer membrane of the nuclear envelope. Nesprins 1 and 2 connect the outer and inner membranes through their interactions with Sun proteins and help to position the nucleus via links to actin filaments. Nesprin 3, which was discovered more recently by Arnoud Sonnenberg and colleagues, is less well characterised. On , the researchers now describe the complex interactions that localise nesprin 3 to the outer nuclear membrane. They show that the last four residues in its C-terminal KASH domain interact with Sun proteins. They also show that nesprin 3 associates with the N-terminal actin-binding domain (ABD) of plectin – a member of the plakin family that regulates actin dynamics. They find that overexpression of plectin's ABD stabilises the actin cytoskeleton and that this, in turn, disrupts the binding of plectin dimers to nesprin 3 – this indicates that actin dynamics influence the plectin–nesprin-3 interaction. As well interacting with nesprin 3 at its N-terminus, plectin can also bind to intermediate filaments via its C-terminus. The authors therefore suggest that the nesprin-3–plectin interaction links the nucleus to the intermediate filament system.
