Members of the nesprin protein family are found in the outer membrane of the nuclear envelope. Their interaction with the inner nuclear membrane proteins SUN1 and SUN2 is crucial in maintaining nuclear structure. Outside the nucleus, nesprins are involved in linking the nuclear envelope to the cytoskeleton. Nesprin-3 is the only family member known to bind intermediate filaments (IFs). How this binding is mediated, and the in vivo effects of knocking out nesprin-3, is investigated on page by Arnoud Sonnenberg and colleagues. The authors demonstrate that, despite being expressed at the nuclear envelope of epidermal and skeletal muscle cells during development, the loss of nesprin-3, rather surprisingly, does not impair zebrafish embryonic development or viability. The lack of nesprin-3 does result in the loss of the dense filamentous keratin network around the nucleus, but this association of IFs with the nuclear periphery does not seem to be crucial for development. The authors further show that amino acids R43 and L44, located in a seven-amino-acid stretch in the first spectrin homology domain of mouse nesprin-3α, are required for it to bind to plectin, which in turn associates with IFs. Nesprin-3, therefore, has an important function in establishing a chain of proteins that connect this cytoskeletal component with the nucleus.
