Neuron type-specific proteomics reveals distinct Shank3 proteoforms in iSPNs and dSPNs lead to striatal synaptopathy in Shank3B^-/- mice.

ABSTRACT: Combinatorial expression of postsynaptic proteins underlies synapse diversity within and between neuron types. 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. To overcome the limitations associated with bulk measures of synaptic protein abundance, 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). Investigation of Shank3B^-/- mice lacking exons 13-16 within the Shank3 gene, reveal distinct Shank3 protein isoform expressio

SUBMITTER: Wang YZ 

PROVIDER: S-EPMC11412912 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature