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Developmental dynamics of the postsynaptic proteome to understand synaptic maturation and dysmaturation

ABSTRACT: 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, which may be involved in changes of synaptic signal transduction. We find that the changes in PSD protein abundance in mouse brains correlate with gene expression levels in postnatal mice and perinatal primates. Proteome analysis of PSD from developing common marmosets (Callithrix jacchus) shows that the changes of PSD composition in mouse brain after 2-week-old occur in the marmoset brain mainly during the neonatal period and continue until adulthood. We also describe the changes of PSD proteome at the late developmental stage of marmoset, which may be involved in synaptic pruning observed in primate brains. The maturation of PSD composition is likely defective in autism spectrum disorder (ASD). 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.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Callithrix Jacchus Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Takehiro Suzuki

LAB HEAD: Naoshi Dohmae

PROVIDER: PXD048549 | Pride | 2024-01-17

REPOSITORIES: Pride

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