title: Genetic mutations strengthen functional association of LAP1 with DYT1 dystonia and muscular dystrophy.
abstract: Lamina-associated polypeptide 1 (LAP1) is a ubiquitously expressed integral protein of the inner nuclear membrane. It interacts physically with lamins, torsinA, emerin and protein phosphatase 1; potentially providing a pivotal mechanism for transducing signals across the inner nuclear membrane. In neurons a functional protein complex is formed, comprising LAP1 and torsinA and in skeletal muscle LAP1 and emerin likewise form a protein complex. Several isoforms of LAP1 have been reported across species. However, in humans only two isoforms have been described, LAP1B and LAP1C. The latter has only recently been reported, but its physiological function and mode of action are not clear. The first TOR1AIP1 (gene encoding LAP1) mutation identified is a single nucleotide deletion resulting in a frameshift and a putative truncated LAP1B protein (Turkish mutation). This has deleterious effects associated with a specific form of muscular dystrophy. A second point mutation, affecting both human LAP1 isoforms, was also recently described. This mutation involves the replacement of a single glutamic acid to alanine at position 482 (Moroccan Mutation), thereby causing severe dystonia, cerebellar atrophy and cardiomyopathy. This review focuses on the recently described human LAP1 isoform (LAP1C), the two recently reported LAP1 mutations and post-translational LAP1 modifications. The latter play an important role in regulating this protein. These scientific contributions strengthen the role of LAP1 in DYT1 dystonia and muscular dystrophy.
authors.affiliation: Laboratório de Neurociências e Sinalização, Centro de Biologia Celular, iBiMED SACS, Universidade de Aveiro, Aveiro 3810-193, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rebelo
authors.affiliation: Laboratório de Neurociências e Sinalização, Centro de Biologia Celular, iBiMED SACS, Universidade de Aveiro, Aveiro 3810-193, Portugal.
authors.forename: Edgar F
authors.initials: EF
authors.lastname: da Cruz E Silva
authors.affiliation: Laboratório de Neurociências e Sinalização, Centro de Biologia Celular, iBiMED SACS, Universidade de Aveiro, Aveiro 3810-193, Portugal. Electronic address: odetecs@ua.pt.
authors.forename: Odete A B
authors.initials: OA
authors.lastname: da Cruz E Silva
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D020821:Dystonic Disorders / Q000235:genetics* / Q000378:metabolism; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*
chemical_list: D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D018832:Molecular Chaperones; C108175:TOR1A protein, human
keywords: Emerin; Lamina associated polypeptide 1; Modifier genes; Nuclear envelope; PP1; Protein phosphatase 1; Torsin A