Intracellular trafficking of emerin, the Emery-Dreifuss muscular dystrophyprotein

Emerin is an integral protein of the inner nuclear membrane that is mutated or not expressed in patients with Emery-Dreifuss muscular dystrophy. Confo cal 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, aminoterminal dom ain 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 mem brane. The transmembrane segment of emerin is not targeted to the inner nuc lear membrane. Fluorescence photobleaching experiments of emerin fused to g reen fluorescent protein demonstrate that the diffusional mobility (D) of e merin is decreased in the inner nuclear membrane (D=0.10+/-0.01 mu m(2)/sec ond) compared to the ER membrane (D=0.32+/-0.01 mu m(2)/second). This is in agreement with a model where integral proteins reach the inner nuclear mem brane by lateral diffusion and are retained there by association with nucle oplasmic components. Some overexpressed emerin-green fluorescent protein al so 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.