Specification of neural circuit architecture shaped by context-dependent patterned LAR-RPTP microexons
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 str...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-02-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45695-0 |
| _version_ | 1827175875113648128 |
|---|---|
| author | Kyung Ah Han Taek-Han Yoon Jinhu Kim Jusung Lee Ju Yeon Lee Gyubin Jang Ji Won Um Jong Kyoung Kim Jaewon Ko |
| author_facet | Kyung Ah Han Taek-Han Yoon Jinhu Kim Jusung Lee Ju Yeon Lee Gyubin Jang Ji Won Um Jong Kyoung Kim Jaewon Ko |
| author_sort | Kyung Ah Han |
| collection | DOAJ |
| description | 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 object-location memory. Activity-triggered alterations of the presynaptic Ptprd meA code in subicular neurons mediates NMDA receptor-mediated postsynaptic responses in CA1 neurons and object-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. |
| first_indexed | 2024-03-07T14:53:03Z |
| format | Article |
| id | doaj.art-f0e12d4eacc64673ac424ad2d9da2c9b |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2025-03-21T04:18:23Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-f0e12d4eacc64673ac424ad2d9da2c9b2024-07-28T11:26:16ZengNature PortfolioNature Communications2041-17232024-02-0115112110.1038/s41467-024-45695-0Specification of neural circuit architecture shaped by context-dependent patterned LAR-RPTP microexonsKyung Ah Han0Taek-Han Yoon1Jinhu Kim2Jusung Lee3Ju Yeon Lee4Gyubin Jang5Ji Won Um6Jong Kyoung Kim7Jaewon Ko8Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST)Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST)Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST)Department of New Biology, DGISTKorea Basic Science Institute, Research Center for Bioconvergence AnalysisDepartment of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST)Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST)Department of New Biology, DGISTDepartment of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST)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 object-location memory. Activity-triggered alterations of the presynaptic Ptprd meA code in subicular neurons mediates NMDA receptor-mediated postsynaptic responses in CA1 neurons and object-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.https://doi.org/10.1038/s41467-024-45695-0 |
| spellingShingle | Kyung Ah Han Taek-Han Yoon Jinhu Kim Jusung Lee Ju Yeon Lee Gyubin Jang Ji Won Um Jong Kyoung Kim Jaewon Ko Specification of neural circuit architecture shaped by context-dependent patterned LAR-RPTP microexons Nature Communications |
| title | Specification of neural circuit architecture shaped by context-dependent patterned LAR-RPTP microexons |
| title_full | Specification of neural circuit architecture shaped by context-dependent patterned LAR-RPTP microexons |
| title_fullStr | Specification of neural circuit architecture shaped by context-dependent patterned LAR-RPTP microexons |
| title_full_unstemmed | Specification of neural circuit architecture shaped by context-dependent patterned LAR-RPTP microexons |
| title_short | Specification of neural circuit architecture shaped by context-dependent patterned LAR-RPTP microexons |
| title_sort | specification of neural circuit architecture shaped by context dependent patterned lar rptp microexons |
| url | https://doi.org/10.1038/s41467-024-45695-0 |
| work_keys_str_mv | AT kyungahhan specificationofneuralcircuitarchitectureshapedbycontextdependentpatternedlarrptpmicroexons AT taekhanyoon specificationofneuralcircuitarchitectureshapedbycontextdependentpatternedlarrptpmicroexons AT jinhukim specificationofneuralcircuitarchitectureshapedbycontextdependentpatternedlarrptpmicroexons AT jusunglee specificationofneuralcircuitarchitectureshapedbycontextdependentpatternedlarrptpmicroexons AT juyeonlee specificationofneuralcircuitarchitectureshapedbycontextdependentpatternedlarrptpmicroexons AT gyubinjang specificationofneuralcircuitarchitectureshapedbycontextdependentpatternedlarrptpmicroexons AT jiwonum specificationofneuralcircuitarchitectureshapedbycontextdependentpatternedlarrptpmicroexons AT jongkyoungkim specificationofneuralcircuitarchitectureshapedbycontextdependentpatternedlarrptpmicroexons AT jaewonko specificationofneuralcircuitarchitectureshapedbycontextdependentpatternedlarrptpmicroexons |