RT Journal Article
SR Electronic
T1 Developmental dynamics of the postsynaptic proteome to understand synaptic maturation and dysmaturation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.05.490828
DO 10.1101/2022.05.05.490828
A1 Takeshi Kaizuka
A1 Takehiro Suzuki
A1 Noriyuki Kishi
A1 Manfred W. Kilimann
A1 Takehiko Ueyama
A1 Masahiko Watanabe
A1 Hideyuki Okano
A1 Naoshi Dohmae
A1 Toru Takumi
YR 2022
UL http://biorxiv.org/content/early/2022/05/06/2022.05.05.490828.abstract
AB The postsynaptic density (PSD) is a protein condensate composed of ∼1,000 proteins beneath the postsynaptic membrane of excitatory synapses. The number, shape, and plasticity of synapses are altered during development. However, the dynamics of synaptic protein composition across development have not been fully understood. Here we show alterations of PSD protein composition in mouse and primate brains during development. Proteins involved in synapse regulation are enriched in the differentially expressed (288 decreased and 267 increased) proteins on mouse PSD after a 2-week-old. We find that the changes in PSD protein abundance in mouse brains correlate with gene expression levels in postnatal mice and perinatal primates. This alteration of PSD composition is likely to be defective in the brains of mouse models or patients with autism spectrum disorder (ASD). Finally, we demonstrate that the brain of the common marmoset (Callithrix jacchus) changes PSD composition after the juvenile period. The alteration of PSD composition after 2-month-old is distinct from that observed in mice. Our results provide a comprehensive architecture of the remodeling of PSD composition across development, which may explain the molecular basics of synapse maturation and the pathology of psychiatric disorders, such as ASD.Competing Interest StatementThe authors have declared no competing interest.