LEM Domain Containing Protein 2 (LEMD2)

Mutations in certain nuclear envelope (NE) proteins cause muscular dystrophies and other disorders, but the disease mechanisms remain unclear. The nuclear envelope transmembrane protein NET25 (Lem2) is a truncated paralog of MAN1, an NE component linked to bone disorders. NET25 and MAN1 share an approximately 40-residue LEM homology domain with emerin, the protein mutated in X-linked Emery-Dreifuss muscular dystrophy. However, roles for NET25 and MAN1 in myogenesis have not yet been described. NET25 depletion causes hyperactivation of extracellular signal-regulated kinase 1/2 at the onset of differentiation, and pharmacological inhibition of this transient overactivation rescues myogenesis. NET25 and emerin have at least partially overlapping functions during myogenic differentiation, which are distinct from those of MAN1.