The Nuclear Envelope Protein, LAP1B, Is a Novel Protein Phosphatase 1 Substrate

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere76788
JournalPloS one
Volume8
Issue number10
DOIs
StatePublished - Oct 7 2013
Externally publishedYes

Fingerprint

Protein Phosphatase 1
phosphoprotein phosphatase
laminae (animals)
Nuclear Envelope
nuclear membrane
Nuclear Proteins
polypeptides
Peptides
Substrates
Proteins
proteins
Dystonia
binding proteins
Carrier Proteins
Nuclear Lamina
Amino Acid Motifs
nuclear proteins
substrate specificity
Substrate Specificity
membrane proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Santos, M., Rebelo, S., Van Kleeff, P. J. M., Kim, C. E., Dauer, W. T., Fardilha, M., ... da Cruz e Silva, E. F. (2013). The Nuclear Envelope Protein, LAP1B, Is a Novel Protein Phosphatase 1 Substrate. PloS one, 8(10), [e76788]. https://doi.org/10.1371/journal.pone.0076788

The Nuclear Envelope Protein, LAP1B, Is a Novel Protein Phosphatase 1 Substrate. / 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.

In: PloS one, Vol. 8, No. 10, e76788, 07.10.2013.

Research output: Contribution to journalArticle

Santos, M, Rebelo, S, Van Kleeff, PJM, Kim, CE, Dauer, WT, Fardilha, M, da Cruz e Silva, OA & da Cruz e Silva, EF 2013, 'The Nuclear Envelope Protein, LAP1B, Is a Novel Protein Phosphatase 1 Substrate', PloS one, vol. 8, no. 10, e76788. https://doi.org/10.1371/journal.pone.0076788
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. / The Nuclear Envelope Protein, LAP1B, Is a Novel Protein Phosphatase 1 Substrate. In: PloS one. 2013 ; Vol. 8, No. 10.
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