Emerin in health and disease

Abstract

Emery-Dreifuss muscular dystrophy (EDMD) is caused by mutations in the genes encoding emerin, lamins A and C and FHL1. Additional EDMD-like syndromes are caused by mutations in nesprins and LUMA. This review will specifically focus on emerin function and the current thinking for how loss or mutations in emerin cause EDMD. Emerin is a well-conserved, ubiquitously expressed protein of the inner nuclear membrane. Emerin has been shown to have diverse functions, including the regulation of gene expression, cell signaling, nuclear structure and chromatin architecture. This review will focus on the relationships between these functions and the EDMD disease phenotype. Additionally it will highlight open questions concerning emerin's roles in cell and nuclear biology and disease.

Networking in the nucleus: a spotlight on LEM-domain proteins

“…Finally, the nucleoplasmic LAP2α preferentially binds and anchors the hypophosphorylated retinoblastoma protein (pRb) in the nucleus, conferring efficient pRb repressor activity [9]. These findings reinforce proposals that LEM-D-associated human diseases arise due to the misregulation of signaling pathways important for stem cell renewal and differentiation [9, 40, 63]. …”

“…These characteristics suggest emerin is dispensable for muscle development, but needed for muscle maintenance. EDMD is also caused by mutations in genes that encode emerin-binding proteins such as A-type lamins and two LINC ( l inks the n ucleoskeleton and c ytoskeleton) complex components named nesprin-1 and nesprin-2 [40–42] [Razafsky and Hodzic, this issue]. Mutations in other widely expressed LEM-D genes also cause tissue-restricted human diseases.…”

Genetic causes of dilated cardiomyopathy

“…Nuclear envelope disorders ( LMNA and EMD ) are an exception in that both laminopathies and emerinopathies cause DCM in association with conduction disease16 36 37 (figure 5) and a risk of ventricular arrhythmia 37–40. Another example is mtDNA gene mutation that causes either mild concentric HCM that evolves through a DCM-like end-phase phenotype,41 or DCM without LV hypertrophy 42.…”

Do lamin A and lamin C have unique roles?

“…Emerin is a protein localized in the inner nuclear membrane that interacts with lamins and is involved in diverse functions, including the regulation of gene expression, cell signaling, nuclear structure, and chromatin architecture (Koch and Holaska 2014). Two of the X-EDMD patients had a deletion mutation while the third was carrying a missense mutation all resulting in reduction of emerin levels.…”