FIGURE 1.

Schematic diagram of the nuclear envelope. Mutations in LMNA encoding A-type nuclear lamins, proteins of the nuclear lamina on the inner aspect of the inner nuclear membrane, cause autosomal dominant EDMD. Mutations in EMD encoding emerin, an integral protein of the inner nuclear membrane, cause X-linked EDMD. Mutations in genes encoding lamina-associated polypeptide 1 (LAP1), LUMA, SUN1, SUN2 have also been linked to EDMD-like phenotypes. Like emerin, LAP1 and LUMA are integral proteins of the inner nuclear membrane that bind to lamins. SUN1 and SUN2 are also integral inner nuclear membrane proteins that bind to lamins and to nesprins, integral proteins of the outer nuclear membrane, within the perinuclear space lume. The interactions between SUNs and nesprins form the LINC complex, which spans the nuclear envelope, connecting the nucleus to actin, to microtubules via motor proteins, such as kinesins, and to intermediate filaments via plectin (not shown) in the cytoplasm of somatic cells. EDMD, Emery–Dreifuss muscular dystrophy; LINC, Linker of Nucleoskeleton and Cytoskeleton.