PPM1G forms a PPP-type phosphatase holoenzyme with B56δ that maintains adherens junction integrity

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Serine/threonine phosphatases require holoenzyme formation for substrate specificity.
• While PPP family phosphatases form holoenzymes, PPM family members were not known to do so.

Purpose of the Study:

• To investigate whether PPM1G, a PPM family member, forms holoenzymes.
• To identify substrates and functions of potential PPM1G-containing holoenzymes.

Main Methods:

• Co-immunoprecipitation to detect protein complex formation.
• Immunofluorescence microscopy for cellular localization studies.
• In vitro phosphatase assays and Western blotting to assess substrate dephosphorylation.

Main Results:

• PPM1G forms a novel holoenzyme complex with the PP2A regulatory subunit B56δ.
• The B56δ subunit directs PPM1G to the cytoplasm, enabling access to specific substrates.
• α-catenin was identified as a novel substrate, dephosphorylated by the PPM1G-B56δ complex at serine 641.
• Dephosphorylation of α-catenin is crucial for adherens junction assembly and preventing aberrant cell migration.

Conclusions:

• PPM1G functions as a holoenzyme, PPM1G-B56δ, revealing a new class of serine/threonine phosphatase complexes.
• The B56δ regulatory subunit dictates substrate accessibility and cellular function of PPM1G.
• This novel holoenzyme plays a critical role in regulating cell adhesion and migration through α-catenin dephosphorylation.