PT  - JOURNAL ARTICLE
AU  - Takeshi Kaizuka
AU  - Takehiro Suzuki
AU  - Noriyuki Kishi
AU  - Manfred W. Kilimann
AU  - Takehiko Ueyama
AU  - Masahiko Watanabe
AU  - Hideyuki Okano
AU  - Naoshi Dohmae
AU  - Toru Takumi
TI  - Developmental dynamics of the postsynaptic proteome to understand synaptic maturation and dysmaturation
AID  - 10.1101/2022.05.05.490828
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.05.490828
4099  - http://biorxiv.org/content/early/2022/05/06/2022.05.05.490828.short
4100  - http://biorxiv.org/content/early/2022/05/06/2022.05.05.490828.full
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.