Prelamin A mediated recruitment of SUN1 to the nuclear envelope directs nuclear positioning in human muscle

Giovanna Lattanzi (1) , Elisabetta Mattioli (1) , Marta Columbaro (1) , Cristina Capanni (1) , Nadir Mario Maraldi (1) , Vittoria Cenni (1) , Katia Scotlandi (1) , Maria Teresa Martino (1) , Luciano Merlini (1) , Stefano Squarzoni (1)

1 CNR

Lamin A is a nuclear lamina constituent expressed in differentiated cells. Mutations in the LMNA gene cause several diseases, including muscular dystrophy and cardiomyopathy. Among nuclear envelope partners of lamin A are SUN1 and SUN2, which mediate nucleo-cytoskeleton interactions critical to the anchorage of nuclei. In this study, we show that differentiating human myoblasts accumulate farnesylated prelamin A, which elicits upregulation and recruitment of SUN1 to the nuclear envelope and favors SUN2 enrichment at the nuclear poles. Indeed, impairment of prelamin A farnesylation alters SUN1 recruitment and SUN2 localization. Moreover, nuclear positioning in myotubes is severely affected in the absence of farnesylated prelamin A. Importantly, reduced prelamin A and SUN1 levels are observed in Emery-Dreifuss muscular dystrophy myoblasts, concomitant with altered myonuclear positioning. These results demonstrate that the interplay between SUN1 and farnesylated prelamin A contributes to nuclear positioning in human myofibers and may be implicated in pathogenetic mechanisms.

Mots clés: muscle differentiation; nuclear positioning; muscular dystrophy; SUN1; prelamin A

Giovanna Lattanzi, Elisabetta Mattioli, Marta Columbaro, Cristina Capanni, Nadir Mario Maraldi, et al.. Prelamin A mediated recruitment of SUN1 to the nuclear envelope directs nuclear positioning in human muscle. Cell Death and Differentiation, 2011, ⟨10.1038/cdd.2010.183⟩. ⟨hal-00614318⟩