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Alternatively spliced mini exon B in PTPRD regulates hippocampal excitatory synapses through trans synaptic PTPRD IL1RAP interaction

ABSTRACT: PTP?, encoded by PTPRD, is implicated in various neurological, psychiatric, and neurodevelopmental disorders, but the underlying mechanisms remain unclear. PTP? trans-synaptically interacts with multiple postsynaptic adhesion molecules, which involves its extracellular alternatively spliced mini-exons, meA and meB. While PTP?-meA functions have been studied in vivo, PTP?-meB has not been studied. Here, we report that, unlike homozygous PTP?-meA-mutant mice, homozygous PTP?-meB-mutant (Ptprd-meB–/–) mice show markedly reduced early postnatal survival. Heterozygous Ptprd-meB+/– male mice show behavioral abnormalities and decreased excitatory synaptic density and transmission in dentate gyrus granule cells (DG-GCs). Proteomic analyses identify decreased postsynaptic density levels of IL1RAP, a known trans-synaptic partner of meB-containing PTP?. Accordingly, IL1RAP-mutant mice show decreased excitatory synaptic transmission in DG-GCs. Ptprd-meB+/– DG interneurons with minimal IL1RAP expression show increased excitatory synaptic density and transmission. Therefore, PTP?-meB is important for survival, synaptic, and behavioral phenotypes and regulates excitatory synapses in cell-type-specific and IL1RAP-dependent manners.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Jin Young Kim

PROVIDER: MSV000094934 | MassIVE | Tue Jun 04 22:21:00 BST 2024

SECONDARY ACCESSION(S): PXD052848

REPOSITORIES: MassIVE

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