title: LUMA interacts with emerin and influences its distribution at the inner nuclear membrane.
abstract: We present here a first characterization of LUMA, an unique integral inner nuclear membrane (INM) protein. LUMA is a highly conserved protein even in some bacteria and shares a PFAM domain of unknown function with orthologs from many species. Assessing LUMA topology by using protease protection of membrane-inserted LUMA and antibody epitope accessibility assays reveals that LUMA contains four transmembrane domains and a large hydrophilic domain located between membrane spans 1 and 2. The large hydrophilic domain is exposed to the perinuclear space whereas both LUMA termini reside cyto- or nucleoplasmically. Nuclear envelope targeting of LUMA mainly depends on the membrane spans. LUMA's transmembrane domains also promote homooligomerization. LUMA binds A- and B-type lamins and depends on A-type lamins for its INM localization. Furthermore, it interacts with emerin. Both downregulation of LUMA and overexpression of dominant-negative acting LUMA fragments causes redistribution of emerin. We propose that LUMA functions as a tetraspanin-like membrane organizer and has the potential to contribute to the pathomechanism of dystrophic diseases, such as Emery-Dreifuss muscular dystrophy.
authors.affiliation: Freie Universität Berlin, Institut für Chemie und Biochemie, Thielallee 63, Berlin, Germany.
authors.forename: Luiza
authors.initials: L
authors.lastname: Bengtsson
authors.forename: Henning
authors.initials: H
authors.lastname: Otto
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015151:Immunoblotting; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008565:Membrane Proteins; D009687:Nuclear Proteins; C092710:emerin