PT  - JOURNAL ARTICLE
AU  - Yi-Zhi Wang
AU  - Tamara Perez-Rosello
AU  - D. James Surmeier
AU  - Jeffrey N. Savas
TI  - Neuron-specific protein expression at striatal excitatory synapses
AID  - 10.1101/2023.03.16.532957
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.03.16.532957
4099  - http://biorxiv.org/content/early/2023/03/17/2023.03.16.532957.short
4100  - http://biorxiv.org/content/early/2023/03/17/2023.03.16.532957.full
AB  - Combinatorial expression of postsynaptic proteins underlies synapse diversity within and between neuron types 1-5. Thus, characterization of neuron-type-specific postsynaptic proteomes is key to obtaining a deeper understanding of discrete synaptic properties and how selective dysfunction manifests in synaptopathies 6-9. To overcome the limitations associated with bulk measures of synaptic protein abundance 6,10, we developed a biotin proximity protein tagging probe to characterize neuron-type-specific postsynaptic proteomes in vivo. We found Shank3 protein isoforms are differentially expressed by direct and indirect pathway spiny projection neurons (dSPNs and iSPNs). Studies in mice lacking Shank3 gene exons 13-16 revealed a robust postsynaptic proteome alteration in iSPNs. We report unexpected cell-type specific synaptic protein isoform expression which could play a key causal role in specifying synapse diversity and selective synapse dysfunction in synaptopathies.Competing Interest StatementThe authors have declared no competing interest.