The phosphatase activity of the PPP2R5D-PP2A holoenzyme modulates liprin-α1 liquid-liquid phase separation.

ABSTRACT: Liprin-α1 is a widely expressed scaffolding protein known to regulate cellular processes such as cell motility and synaptic transmission through assembly of localized higher-order molecular complexes. However, the dynamic regulation of these complexes remains poorly understood. Liquid-liquid phase separation (LLPS) is a process that concentrates proteins into cellular nanodomains, facilitating efficient spatiotemporal signaling. Whether liprin-α1 undergoes regulated LLPS remains unclear. Mass spectrometry-based interactomics identified PPP2R5D, the regulatory B56δ subunit of PP2A, as a liprin-α1 interaction partner via a canonical short linear motif (SLiM) in its N terminal dimerization domain. Mutation of SLiM4 nearly abolished liprin-α1 interaction with PP2A holoenzyme and resulted in a

SUBMITTER: Mayer A 

PROVIDER: S-EPMC12273559 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature