Control of Emi2 activity and stability through Mos-mediated recruitment of PP2A

Area of Science:

• Cellular biology
• Molecular and developmental biology
• Reproductive biology

Background:

• Vertebrate eggs arrest in meiosis II via cytostatic factor (CSF), which inhibits the anaphase-promoting complex (APC).
• Mos, a key CSF component, was known to promote Rsk-mediated phosphorylation of the APC inhibitor Emi2/Erp1.

Purpose of the Study:

• To elucidate the molecular mechanism by which Mos promotes CSF arrest.
• To define how Rsk phosphorylation of Emi2 influences its interaction with other regulatory proteins.

Main Methods:

• Investigated the interaction between Rsk-phosphorylated Emi2 and protein phosphatase 2A (PP2A).
• Utilized Emi2 mutants to assess the role of specific phosphorylation sites and PP2A binding in Mos-mediated regulation.
• Analyzed the effect of PP2A binding on Emi2 stability and APC interaction.

Main Results:

• Rsk phosphorylation of Emi2 enhances its binding to PP2A.
• Specific Emi2 residues adjacent to the Rsk phosphorylation site are critical for PP2A interaction.
• An Emi2 mutant deficient in PP2A binding, despite retaining Rsk phosphorylation, was unresponsive to Mos.
• Bound PP2A dephosphorylates distinct Cdc2 phosphorylation sites on Emi2, modulating its stability and APC binding.

Conclusions:

• Protein phosphorylation of Emi2 by Rsk recruits PP2A, establishing a molecular mechanism for Mos action in CSF arrest.
• This study reveals an unconventional regulatory pathway where phosphorylation triggers phosphatase recruitment for targeted dephosphorylation.
• The findings clarify the intricate regulation of Emi2, essential for maintaining meiotic arrest in vertebrate eggs.