ASPPs multimerize protein phosphatase 1.

Area of Science:

• Molecular biology
• Cell biology
• Biochemistry

Background:

• Protein Phosphatase 1 (PP1) activity is regulated by numerous subunits, but their functions remain unclear.
• Ankyrin repeat, SH3-domain, and Proline-rich region containing Proteins (ASPPs) are known to bind and localize PP1 to cell-cell junctions.

Purpose of the Study:

• To investigate the mechanism by which ASPPs regulate PP1 activity at cell-cell junctions.
• To explore the role of ASPP ankyrin repeats in PP1 binding stoichiometry and function.

Main Methods:

• Utilized missense mutations in ASPP ankyrin repeats identified through genetic screening in *Caenorhabditis elegans*.
• Assessed PP1 binding stoichiometry to wild-type and mutant ASPPs.
• Investigated the functional rescue of mutant ASPPs by inducing PP1 oligomerization *in vivo*.

Main Results:

• ASPPs bind Protein Phosphatase 1 (PP1) in superstoichiometric amounts.
• Specific missense mutations within the ankyrin repeats of ASPPs decrease the stoichiometry of PP1 binding.
• Restoring PP1 oligomerization rescued the function of mutant ASPPs in *Caenorhabditis elegans*.

Conclusions:

• ASPPs function by multimerizing PP1, creating a concentrated phosphatase activity hub at cell-cell junctions.
• The ankyrin repeat domain of ASPPs is critical for establishing high-stoichiometry PP1 binding.
• This mechanism highlights a novel regulatory strategy for controlling PP1 activity in cellular processes.