한빛사논문
Kyung Ah Han1,2,6, Taek-Han Yoon1,6, Jinhu Kim1, Ju Sung Lee3, Ju Yeon Lee4, Gyubin Jang1,2, Ji Won Um1,2, Jong Kyoung Kim3,5 & Jaewon Ko1,2
1Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea.
2Center for Synapse Diversity and Specificity, DGIST, Daegu 42988, Korea.
3Department of New Biology, DGIST, Daegu 42988, Korea.
4Korea Basic Science Institute, Research Center for Bioconvergence Analysis, Cheongju 28119, Korea.
5Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea.
6These authors contributed equally: Kyung Ah Han, Taek-Han Yoon
Corresponding author : Correspondence to Jaewon Ko.
Abstract
LAR-RPTPs are evolutionarily conserved presynaptic cell-adhesion molecules that orchestrate multifarious synaptic adhesion pathways. Extensive alternative splicing of LAR-RPTP mRNAs may produce innumerable LAR-RPTP isoforms that act as regulatory “codes” for determining the identity and strength of specific synapse signaling. However, no direct evidence for this hypothesis exists. Here, using targeted RNA sequencing, we detected LAR-RPTP mRNAs in diverse cell types across adult male mouse brain areas. We found pronounced cell-type–specific patterns of two microexons, meA and meB, in Ptprd mRNAs. Moreover, diverse neural circuits targeting the same neuronal populations were dictated by the expression of different Ptprd variants with distinct inclusion patterns of microexons. Furthermore, conditional ablation of Ptprd meA+ variants at presynaptic loci of distinct hippocampal circuits impaired distinct modes of synaptic transmission and objection-location memory. Activity-triggered alterations of the presynaptic Ptprd meA code in subicular neurons mediates NMDA receptor-mediated postsynaptic responses in CA1 neurons and objection-location memory. Our data provide the evidence of cell-type- and/or circuit-specific expression patterns in vivo and physiological functions of LAR-RPTP microexons that are dynamically regulated.
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