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.
Highlights
Reversible protein phosphorylation is a major mechanism controlling key intracellular events that are essential for cell health and viability [1,2,3]
Most phosphatase 1 (PP1) binding proteins interact with the PP1 catalytic subunit through a conserved PP1 binding motif termed the RVxF motif, which has the consensus sequence [R/K] XA(0-1) [V/I] XB [F/W], where XA is any amino acid and XB is any amino acid except proline [14]
One of the novel PP1 regulators isolated in the three independent yeast two-hybrid (YTH) screens was torsinA interacting protein 1 (TOR1AIP1) or lamina associated polypeptide 1B (LAP1B)
Summary
Reversible protein phosphorylation is a major mechanism controlling key intracellular events that are essential for cell health and viability [1,2,3]. Most PP1 binding proteins interact with the PP1 catalytic subunit through a conserved PP1 binding motif termed the RVxF motif, which has the consensus sequence [R/K] XA(0-1) [V/I] XB [F/W], where XA is any amino acid and XB is any amino acid except proline [14]. The binding of PP1 to regulatory proteins through the RVxF motif does not cause major effects on the conformation and activity of PP1, but mediates the initial anchoring of regulatory subunits and thereby promotes the interaction at secondary binding sites [7,16,17]. One of the novel PP1 regulators isolated in the three independent YTH screens was torsinA interacting protein 1 (TOR1AIP1) or lamina associated polypeptide 1B (LAP1B). The functional relevance of this complex was pursued and we determined that LAP1B is dephosphorylated by PP1 in vitro
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
