title: Nuclear membrane protein emerin: roles in gene regulation, actin dynamics and human disease.
abstract: Loss of emerin, a nuclear membrane protein, causes Emery-Dreifuss muscular dystrophy (EDMD), characterized by muscle weakening, contractures of major tendons and potentially lethal cardiac conduction system defects. Emerin has a LEM-domain and therefore binds barrier-to-autointegration factor (BAF), a conserved chromatin protein essential for cell division. BAF recruits emerin to chromatin and regulates higher-order chromatin structure during nuclear assembly. Emerin also binds filaments formed by A-type lamins, mutations in which also cause EDMD. Other partners for emerin include nesprin-1alpha and transcriptional regulators such as germ cell-less (GCL). The binding affinities of these partners range from 4nM (nesprin-1alpha) to 200 nM (BAF), and are physiologically significant. Biochemical studies therefore provide a valid means to predict the properties of emerin-lamin complexes in vivo. Emerin and lamin A together form stable complexes with either BAF or GCL in vitro. BAF, however, competes with GCL for binding to emerin in vitro. These and additional partners, notably actin and nuclear myosin II, suggest disease-relevant roles for emerin in gene regulation and the mechanical interity of the nucleus.
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Wilson
authors.forename: James M
authors.initials: JM
authors.lastname: Holaska
authors.forename: Rocio
authors.initials: R
authors.lastname: Montes de Oca
authors.forename: Kathryn
authors.initials: K
authors.lastname: Tifft
authors.forename: Michael
authors.initials: M
authors.lastname: Zastrow
authors.forename: Miriam
authors.initials: M
authors.lastname: Segura-Totten
authors.forename: Malini
authors.initials: M
authors.lastname: Mansharamani
authors.forename: Luiza
authors.initials: L
authors.lastname: Bengtsson
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D009136:Muscular Dystrophies / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins; D013946:Thymopoietins / Q000502:physiology*
chemical_list: D000199:Actins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D013946:Thymopoietins; C092710:emerin