The Nuclear Envelope Protein,LAP1B,Is a Novel Protein Phosphatase 1 Substrate |
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| Authors: | Mariana Santos Sandra Rebelo Paula J. M. Van Kleeff Connie E. Kim William T. Dauer Margarida Fardilha Odete A. da Cruz e Silva Edgar F. da Cruz e Silva |
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| Affiliation: | 1. Health Sciences Department, Centre for Cell Biology, Neuroscience Laboratory, University of Aveiro, Aveiro, Portugal.; 2. Health Sciences Department, Centre for Cell Biology, Signal Transduction Laboratory, University of Aveiro, Aveiro, Portugal.; 3. Departments of Neurology and Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.; Institute of Enzymology of the Hungarian Academy of Science, Hungary, |
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| 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. |
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