title: The nuclear envelope protein, LAP1B, is a novel protein phosphatase 1 substrate.
abstract: Protein phosphatase 1 (PP1) binding proteins are quintessential regulators, determining substrate specificity and defining subcellular localization and activity of the latter. Here, we describe a novel PP1 binding protein, the nuclear membrane protein lamina associated polypeptide 1B (LAP1B), which interacts with the DYT1 dystonia protein torsinA. The PP1 binding domain in LAP1B was here identified as the REVRF motif at amino acids 55-59. The LAP1B:PP1 complex can be immunoprecipitated from cells in culture and rat cortex and the complex was further validated by yeast co-transformations and blot overlay assays. PP1, which is enriched in the nucleus, binds to the N-terminal nuclear domain of LAP1B, as shown by immunocolocalization and domain specific binding studies. PP1 dephosphorylates LAP1B, confirming the physiological relevance of this interaction. These findings place PP1 at a key position to participate in the pathogenesis of DYT1 dystonia and related nuclear envelope-based diseases.
authors.affiliation: Health Sciences Department, Centre for Cell Biology, Neuroscience Laboratory, University of Aveiro, Aveiro, Portugal.
authors.forename: Mariana
authors.initials: M
authors.lastname: Santos
authors.forename: Sandra
authors.initials: S
authors.lastname: Rebelo
authors.forename: Paula J M
authors.initials: PJ
authors.lastname: Van Kleeff
authors.forename: Connie E
authors.initials: CE
authors.lastname: Kim
authors.forename: William T
authors.initials: WT
authors.lastname: Dauer
authors.forename: Margarida
authors.initials: M
authors.lastname: Fardilha
authors.forename: Odete A
authors.initials: OA
authors.lastname: da Cruz E Silva
authors.forename: Edgar F
authors.initials: EF
authors.lastname: da Cruz E Silva
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000378:metabolism; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D020798:Two-Hybrid System Techniques
chemical_list: D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C486250:TOR1AIP1 protein, human; C093127:TOR1AIP1 protein, rat; D054645:Protein Phosphatase 1