Emerin is an integral
protein of the inner nuclear membrane that is mutated or not expressed in patients with
Emery-Dreifuss muscular dystrophy. Confocal immunofluorescence microscopy studies of the intracellular targeting of truncated forms of
emerin, some of which are found in patients with
Emery-Dreifuss muscular dystrophy, show that the nucleoplasmic, amino-terminal domain is necessary and sufficient for nuclear retention. When this domain is fused to a transmembrane segment of an
integral membrane protein of the ER/plasma membrane, the chimeric
protein is localized in the inner nuclear membrane. The transmembrane segment of
emerin is not targeted to the inner nuclear membrane. Fluorescence photobleaching experiments of
emerin fused to
green fluorescent protein demonstrate that the diffusional mobility (D) of
emerin is decreased in the inner nuclear membrane (D=0.10+/-0.01 microm2/second) compared to the ER membrane (D=0.32+/-0.01 microm2/second). This is in agreement with a model where integral
proteins reach the inner nuclear membrane by lateral diffusion and are retained there by association with nucleoplasmic components. Some overexpressed
emerin-
green fluorescent protein also reaches the plasma membrane of transfected cells, where its diffusion is similar to that in the inner nuclear membrane, suggesting that
emerin may also associate with non-nuclear structures.