Emerin is an essential LEM (LAP2,
Emerin, MAN1) domain protein in metazoans and an
integral membrane protein associated with inner and outer nuclear membranes. Mutations in the human EMD gene coding for
emerin result in the rare
genetic disorder: Emery⁻Dreifuss
muscular dystrophy type 1 (
EDMD1). This disease belongs to a broader group called
laminopathies-a heterogeneous group of rare
genetic disorders affecting tissues of mesodermal origin.
EDMD1 phenotype is characterized by progressive muscle wasting,
contractures of the elbow and Achilles tendons, and
cardiac conduction defects.
Emerin is involved in many cellular and intranuclear processes through interactions with several partners:
lamins; barrier-to-autointegration factor (BAF), β-
catenin, actin, and
tubulin. Our study demonstrates the presence of the
emerin fraction which associates with mitotic spindle microtubules and centrosomes during mitosis and colocalizes during early mitosis with
lamin A/C, BAF, and membranes at the mitotic spindle. Transfection studies with cells expressing EGFP-
emerin protein demonstrate that the
emerin fusion
protein fraction also localizes to centrosomes and mitotic spindle microtubules during mitosis. Transient expression of
emerin deletion mutants revealed that the resulting phenotypes vary and are mutant dependent. The most frequent phenotypes include aberrant nuclear shape,
tubulin network mislocalization, aberrant mitosis, and mislocalization of centrosomes.
Emerin deletion mutants demonstrated different
chromatin binding capacities in an in vitro nuclear assembly assay and
chromatin-binding properties correlated with the strength of phenotypic alteration in transfected cells. Aberrant
tubulin staining and microtubule network phenotype appearance depended on the presence of the
tubulin binding region in the expressed deletion mutants. We believe that the association with
tubulin might help to "deliver"
emerin and associated membranes to decondensing
chromatin. Preliminary analyses of cells from Polish patients with
EDMD1 revealed that for several mutations thought to be null for
emerin protein, a truncated
emerin protein was present. We infer that the
EDMD1 phenotype may be strengthened by the toxicity of truncated
emerin expressed in patients with certain
nonsense mutations in EMD.