Exploring the function of GKAP phosphorylation through biochemically reconstituted PSD

Abstract

Membraneless organelles formed by phase separation/transition of proteins and nucleic acids are increasingly recognized to play diverse cellular functions. Whether and, if yes, how membraneless organelles also undergo regulated fusion and fission events as membrane-based organelles do are much less understood. Here, I use the postsynaptic density protein condensates as a paradigm, that membraneless organelles can undergo phosphorylation-dependent dynamic fusion and fission events. Without phosphorylation of SAPAP, the upper and lower layers of PSD proteins form two immiscible sub-compartments in a phase-in-phase organization with SAPAP to maintain the two compartments together. Phosphorylation of SAPAP by CaMKⅡ leads to fusion of the two sub-compartments into one PSD condensate accompanied with an increased receptor density in the condensate. Dephosphorylation of SAPAP causes the fused PSD condensate splitting into two immiscible sub-compartments. Thus, I found that the membraneless organelles like PSD, analogous to membrane-based organelles, can also undergo regulated fusion and fission.

Date of Award	2023
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Zilong WEN (Supervisor) & Mingjie ZHANG (Supervisor)