Expert Reviews in Molecular Medicine

 



Review Article

Nesprins: intracellular scaffolds that maintain cell architecture and coordinate cell function?


Derek T. Warren a1, Qiuping Zhang a1, Peter L Weissberg a1 and Catherine M. Shanahan a1c1
a1 Department of Medicine, ACCI, Level 6, Box 110, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK.

Abstract

Nesprins are a recently discovered family of ubiquitously expressed intracellular proteins. Through alternative transcriptional initiation, termination and splicing, two genes – nesprin-1 and nesprin-2 (also known as syne-1 and syne-2) – give rise to many protein isoforms that vary markedly in size. The largest of these isoforms comprise a C-terminal transmembrane domain (the KLS domain) linked by a spectrin-repeat rod domain to an N-terminal paired, actin-binding, calponin-homology domain. This structure suggests that they are well suited to orchestrate signalling between cell membranes and the cytoskeleton. Other isoforms have variable lengths of this rod domain linked to either end of the protein. Smaller isoforms with the KLS domain are localised at the inner nuclear membrane, where they bind lamin A/C and emerin. Larger nesprin isoforms link the outer nuclear membrane with intracellular organelles and the actin cytoskeleton and are thought to regulate nuclear anchorage and organelle migration. Thus, nesprins might have a variety of fundamental roles in cells, particularly muscle cells where they are highly expressed. We speculate that nesprin mutations might contribute to a broad range of human disease syndromes, including laminopathies.


Key Words: nesprins; nuclear envelope; actin; laminopathy; lamin; emerin; muscle; syne proteins; nuance; enaptin.

Correspondence:
c1 Department of Medicine, ACCI, Level 6, Box 110, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK. Tel: +44 (0)1223 331504; Fax: +44 (0)1223 331505 E-mail: cs131@mole.bio.cam.ac.uk