Nesprins, but not sun proteins, switch isoforms at the nuclear envelope during muscle development

Nesprins are a family of nuclear transmembrane proteins anchored via Sun proteins to the nuclear membrane. Analysis of nesprins during human muscle development revealed an increase in nesprin‐1‐giant during early myogenesis in vitro. During the transition from immature to mature muscle fibres in vivo, nesprin‐2 partly replaced nesprin‐1 at the nuclear envelope and short nesprin isoforms became dominant. Sun1 and Sun2 proteins remained unchanged during this fibre maturation. In emerin‐negative skin fibroblasts, nesprin‐2‐giant was relocated from the nuclear envelope to the cytoplasm, not to the endoplasmic reticulum, while nesprin‐1 remained at the nuclear envelope. In emerin‐negative keratinocytes lacking nesprin‐1, nesprin‐2 remained at the nuclear envelope. HeLa cell nuclear envelopes lacked nesprin‐1, which was the dominant form in myoblasts, while a novel 130‐kD nesprin‐2 isoform dominated Ntera‐2 cells. The results suggest the possibility of isoform‐specific and tissue‐specific roles for nesprins in nuclear positioning. Developmental Dynamics 239:998–1009, 2010. © 2010 Wiley‐Liss, Inc.