The nuclear envelope protein, LAP1B, is a novel protein phosphatase 1 substrate

• Published in: PloS one Vol. 8; no. 10; p. e76788
• Main Authors: Santos, Mariana, Rebelo, Sandra, Van Kleeff, Paula J M, Kim, Connie E, Dauer, William T, Fardilha, Margarida, da Cruz E Silva, Odete A, da Cruz E Silva, Edgar F
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07-10-2013; Public Library of Science (PLoS)
• Subjects: Amino Acid Motifs - genetics; Amino Acid Sequence; Amino acids; Animals; Base Sequence; Brain; Cell culture; Cell Line, Tumor; Cerebral Cortex - metabolism; Chlorocebus aethiops; COS Cells; Cytoskeletal Proteins; Developmental biology; Dystonia; Health sciences; HEK293 Cells; HeLa Cells; Humans; Immunoblotting; Immunoglobulins; Immunoprecipitation; Kinases; Laboratories; Localization; Membrane proteins; Membrane Proteins - genetics; Membrane Proteins - metabolism; Molecular Sequence Data; Mutation; Neurosciences; Nuclear Envelope - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Nuclei; Pathogenesis; Phosphatase; Phosphatases; Phosphoprotein phosphatase; Phosphorylation; Polypeptides; Protein Binding; Protein phosphatase; Protein Phosphatase 1 - genetics; Protein Phosphatase 1 - metabolism; Proteins; Rats; Rats, Wistar; Regulators; Sequence Homology, Amino Acid; Signal transduction; Substrate Specificity; Substrates; Two-Hybrid System Techniques; Viral envelope proteins; Yeast; Ann Arbor Michigan; United States > US; Portugal; Michigan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0076788

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.