RT Journal Article
SR Electronic
T1 Bi-directional protein-protein interactions control liquid-liquid phase separation of PSD-95 and its interaction partners
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.03.433781
DO 10.1101/2021.03.03.433781
A1 Nikolaj Riis Christensen
A1 Christian Parsbæk Pedersen
A1 Vita Sereikaite
A1 Jannik Nedergaard Pedersen
A1 Maria Vistrup-Parry
A1 Andreas Toft Sørensen
A1 Daniel Otzen
A1 Lise Arleth
A1 Kaare Teilum
A1 Kenneth L. Madsen
A1 Kristian Strømgaard
YR 2021
UL http://biorxiv.org/content/early/2021/03/03/2021.03.03.433781.abstract
AB The organization of the postsynaptic density (PSD), a protein-dense semi-membraneless organelle, is mediated by numerous specific protein-protein interactions (PPIs) which constitute a functional post-synapse. Postsynaptic density protein 95 (PSD-95) interacts with a manifold of proteins, including the C-terminal of transmembrane AMPA receptor (AMAPR) regulatory proteins (TARPs). Here, we uncover the minimal essential peptide responsible for the stargazin (TARP-γ2) mediated liquid-liquid phase separation (LLPS) formation of PSD-95 and other key protein constituents of the PSD. Furthermore, we find that pharmacological inhibitors of PSD-95 can facilitate formation of LLPS. We found that in some cases LLPS formation is dependent on multivalent interactions while in other cases short peptides carrying a high charge are sufficient to promote LLPS in complex systems. This study offers a new perspective on PSD-95 interactions and their role in LLPS formation, while also considering the role of affinity over multivalency in LLPS systems.Competing Interest StatementThe authors have declared no competing interest.