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Transsynaptic cerebellin 4–neogenin 1 signaling mediates LTP in the mouse dentate gyrus
Five decades ago, long-term potentiation (LTP) of synaptic transmission was discovered at entorhinal cortex→dentate gyrus (EC→DG) synapses, but the molecular determinants of EC→DG LTP remain largely unknown. Here, we show that the presynaptic neurexin–ligand cerebellin-4 (Cbln4) is highly expressed...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171784/ https://www.ncbi.nlm.nih.gov/pubmed/35544694 http://dx.doi.org/10.1073/pnas.2123421119 |
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author | Liakath-Ali, Kif Polepalli, Jai S. Lee, Sung-Jin Cloutier, Jean-Francois Südhof, Thomas C. |
author_facet | Liakath-Ali, Kif Polepalli, Jai S. Lee, Sung-Jin Cloutier, Jean-Francois Südhof, Thomas C. |
author_sort | Liakath-Ali, Kif |
collection | PubMed |
description | Five decades ago, long-term potentiation (LTP) of synaptic transmission was discovered at entorhinal cortex→dentate gyrus (EC→DG) synapses, but the molecular determinants of EC→DG LTP remain largely unknown. Here, we show that the presynaptic neurexin–ligand cerebellin-4 (Cbln4) is highly expressed in the entorhinal cortex and essential for LTP at EC→DG synapses, but dispensable for basal synaptic transmission at these synapses. Cbln4, when bound to cell-surface neurexins, forms transcellular complexes by interacting with postsynaptic DCC (deleted in colorectal cancer) or neogenin-1. DCC and neogenin-1 act as netrin and repulsive guidance molecule-a (RGMa) receptors that mediate axon guidance in the developing brain, but their binding to Cbln4 raised the possibility that they might additionally function in the mature brain as postsynaptic receptors for presynaptic neurexin/Cbln4 complexes, and that as such receptors, DCC or neogenin-1 might mediate EC→DG LTP that depends on Cbln4. Indeed, we observed that neogenin-1, but not DCC, is abundantly expressed in dentate gyrus granule cells, and that postsynaptic neogenin-1 deletions in dentate granule cells blocked EC→DG LTP, but again did not affect basal synaptic transmission similar to the presynaptic Cbln4 deletions. Thus, binding of presynaptic Cbln4 to postsynaptic neogenin-1 renders EC→DG synapses competent for LTP, but is not required for establishing these synapses or for otherwise enabling their function. |
format | Online Article Text |
id | pubmed-9171784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-91717842022-11-15 Transsynaptic cerebellin 4–neogenin 1 signaling mediates LTP in the mouse dentate gyrus Liakath-Ali, Kif Polepalli, Jai S. Lee, Sung-Jin Cloutier, Jean-Francois Südhof, Thomas C. Proc Natl Acad Sci U S A Biological Sciences Five decades ago, long-term potentiation (LTP) of synaptic transmission was discovered at entorhinal cortex→dentate gyrus (EC→DG) synapses, but the molecular determinants of EC→DG LTP remain largely unknown. Here, we show that the presynaptic neurexin–ligand cerebellin-4 (Cbln4) is highly expressed in the entorhinal cortex and essential for LTP at EC→DG synapses, but dispensable for basal synaptic transmission at these synapses. Cbln4, when bound to cell-surface neurexins, forms transcellular complexes by interacting with postsynaptic DCC (deleted in colorectal cancer) or neogenin-1. DCC and neogenin-1 act as netrin and repulsive guidance molecule-a (RGMa) receptors that mediate axon guidance in the developing brain, but their binding to Cbln4 raised the possibility that they might additionally function in the mature brain as postsynaptic receptors for presynaptic neurexin/Cbln4 complexes, and that as such receptors, DCC or neogenin-1 might mediate EC→DG LTP that depends on Cbln4. Indeed, we observed that neogenin-1, but not DCC, is abundantly expressed in dentate gyrus granule cells, and that postsynaptic neogenin-1 deletions in dentate granule cells blocked EC→DG LTP, but again did not affect basal synaptic transmission similar to the presynaptic Cbln4 deletions. Thus, binding of presynaptic Cbln4 to postsynaptic neogenin-1 renders EC→DG synapses competent for LTP, but is not required for establishing these synapses or for otherwise enabling their function. National Academy of Sciences 2022-05-11 2022-05-17 /pmc/articles/PMC9171784/ /pubmed/35544694 http://dx.doi.org/10.1073/pnas.2123421119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Liakath-Ali, Kif Polepalli, Jai S. Lee, Sung-Jin Cloutier, Jean-Francois Südhof, Thomas C. Transsynaptic cerebellin 4–neogenin 1 signaling mediates LTP in the mouse dentate gyrus |
title | Transsynaptic cerebellin 4–neogenin 1 signaling mediates LTP in the mouse dentate gyrus |
title_full | Transsynaptic cerebellin 4–neogenin 1 signaling mediates LTP in the mouse dentate gyrus |
title_fullStr | Transsynaptic cerebellin 4–neogenin 1 signaling mediates LTP in the mouse dentate gyrus |
title_full_unstemmed | Transsynaptic cerebellin 4–neogenin 1 signaling mediates LTP in the mouse dentate gyrus |
title_short | Transsynaptic cerebellin 4–neogenin 1 signaling mediates LTP in the mouse dentate gyrus |
title_sort | transsynaptic cerebellin 4–neogenin 1 signaling mediates ltp in the mouse dentate gyrus |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171784/ https://www.ncbi.nlm.nih.gov/pubmed/35544694 http://dx.doi.org/10.1073/pnas.2123421119 |
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