LAR receptor phospho-tyrosine phosphatases regulate NMDA-receptor responses
LAR-type receptor phosphotyrosine-phosphatases (LAR-RPTPs) are presynaptic adhesion molecules that interact trans-synaptically with multitudinous postsynaptic adhesion molecules, including SliTrks, SALMs, and TrkC. Via these interactions, LAR-RPTPs are thought to function as synaptogenic wiring mole...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/53406 |
| _version_ | 1811181012695121920 |
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| author | Alessandra Sclip Thomas C Südhof |
| author_facet | Alessandra Sclip Thomas C Südhof |
| author_sort | Alessandra Sclip |
| collection | DOAJ |
| description | LAR-type receptor phosphotyrosine-phosphatases (LAR-RPTPs) are presynaptic adhesion molecules that interact trans-synaptically with multitudinous postsynaptic adhesion molecules, including SliTrks, SALMs, and TrkC. Via these interactions, LAR-RPTPs are thought to function as synaptogenic wiring molecules that promote neural circuit formation by mediating the establishment of synapses. To test the synaptogenic functions of LAR-RPTPs, we conditionally deleted the genes encoding all three LAR-RPTPs, singly or in combination, in mice before synapse formation. Strikingly, deletion of LAR-RPTPs had no effect on synaptic connectivity in cultured neurons or in vivo, but impaired NMDA-receptor-mediated responses. Deletion of LAR-RPTPs decreased NMDA-receptor-mediated responses by a trans-synaptic mechanism. In cultured neurons, deletion of all LAR-RPTPs led to a reduction in synaptic NMDA-receptor EPSCs, without changing the subunit composition or the protein levels of NMDA-receptors. In vivo, deletion of all LAR-RPTPs in the hippocampus at birth also did not alter synaptic connectivity as measured via AMPA-receptor-mediated synaptic responses at Schaffer-collateral synapses monitored in juvenile mice, but again decreased NMDA-receptor mediated synaptic transmission. Thus, LAR-RPTPs are not essential for synapse formation, but control synapse properties by regulating postsynaptic NMDA-receptors via a trans-synaptic mechanism that likely involves binding to one or multiple postsynaptic ligands. |
| first_indexed | 2024-04-11T09:11:12Z |
| format | Article |
| id | doaj.art-12cc09212fc24b9e920a127195f31280 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:11:12Z |
| publishDate | 2020-01-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-12cc09212fc24b9e920a127195f312802022-12-22T04:32:29ZengeLife Sciences Publications LtdeLife2050-084X2020-01-01910.7554/eLife.53406LAR receptor phospho-tyrosine phosphatases regulate NMDA-receptor responsesAlessandra Sclip0https://orcid.org/0000-0002-9313-4176Thomas C Südhof1Department of Cellular and Molecular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United StatesDepartment of Cellular and Molecular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United StatesLAR-type receptor phosphotyrosine-phosphatases (LAR-RPTPs) are presynaptic adhesion molecules that interact trans-synaptically with multitudinous postsynaptic adhesion molecules, including SliTrks, SALMs, and TrkC. Via these interactions, LAR-RPTPs are thought to function as synaptogenic wiring molecules that promote neural circuit formation by mediating the establishment of synapses. To test the synaptogenic functions of LAR-RPTPs, we conditionally deleted the genes encoding all three LAR-RPTPs, singly or in combination, in mice before synapse formation. Strikingly, deletion of LAR-RPTPs had no effect on synaptic connectivity in cultured neurons or in vivo, but impaired NMDA-receptor-mediated responses. Deletion of LAR-RPTPs decreased NMDA-receptor-mediated responses by a trans-synaptic mechanism. In cultured neurons, deletion of all LAR-RPTPs led to a reduction in synaptic NMDA-receptor EPSCs, without changing the subunit composition or the protein levels of NMDA-receptors. In vivo, deletion of all LAR-RPTPs in the hippocampus at birth also did not alter synaptic connectivity as measured via AMPA-receptor-mediated synaptic responses at Schaffer-collateral synapses monitored in juvenile mice, but again decreased NMDA-receptor mediated synaptic transmission. Thus, LAR-RPTPs are not essential for synapse formation, but control synapse properties by regulating postsynaptic NMDA-receptors via a trans-synaptic mechanism that likely involves binding to one or multiple postsynaptic ligands.https://elifesciences.org/articles/53406LAR-RPTPspresynaptic cell-adhesion moleculessynaptic transmissionsynapse formationhippocampal circuitNMDA receptors |
| spellingShingle | Alessandra Sclip Thomas C Südhof LAR receptor phospho-tyrosine phosphatases regulate NMDA-receptor responses eLife LAR-RPTPs presynaptic cell-adhesion molecules synaptic transmission synapse formation hippocampal circuit NMDA receptors |
| title | LAR receptor phospho-tyrosine phosphatases regulate NMDA-receptor responses |
| title_full | LAR receptor phospho-tyrosine phosphatases regulate NMDA-receptor responses |
| title_fullStr | LAR receptor phospho-tyrosine phosphatases regulate NMDA-receptor responses |
| title_full_unstemmed | LAR receptor phospho-tyrosine phosphatases regulate NMDA-receptor responses |
| title_short | LAR receptor phospho-tyrosine phosphatases regulate NMDA-receptor responses |
| title_sort | lar receptor phospho tyrosine phosphatases regulate nmda receptor responses |
| topic | LAR-RPTPs presynaptic cell-adhesion molecules synaptic transmission synapse formation hippocampal circuit NMDA receptors |
| url | https://elifesciences.org/articles/53406 |
| work_keys_str_mv | AT alessandrasclip larreceptorphosphotyrosinephosphatasesregulatenmdareceptorresponses AT thomascsudhof larreceptorphosphotyrosinephosphatasesregulatenmdareceptorresponses |