Cargando…
Engineered adhesion molecules drive synapse organization
In multicellular organisms, cell-adhesion molecules connect cells into tissues and mediate intercellular signaling between these cells. In vertebrate brains, synaptic cell-adhesion molecules (SAMs) guide the formation, specification, and plasticity of synapses. Some SAMs, when overexpressed in cultu...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934208/ https://www.ncbi.nlm.nih.gov/pubmed/36638214 http://dx.doi.org/10.1073/pnas.2215905120 |
_version_ | 1784889833484713984 |
---|---|
author | Hale, W. Dylan Südhof, Thomas C. Huganir, Richard L. |
author_facet | Hale, W. Dylan Südhof, Thomas C. Huganir, Richard L. |
author_sort | Hale, W. Dylan |
collection | PubMed |
description | In multicellular organisms, cell-adhesion molecules connect cells into tissues and mediate intercellular signaling between these cells. In vertebrate brains, synaptic cell-adhesion molecules (SAMs) guide the formation, specification, and plasticity of synapses. Some SAMs, when overexpressed in cultured neurons or in heterologous cells co-cultured with neurons, drive formation of synaptic specializations onto the overexpressing cells. However, genetic deletion of the same SAMs from neurons often has no effect on synapse numbers, but frequently severely impairs synaptic transmission, suggesting that most SAMs control the function and plasticity of synapses (i.e., organize synapses) instead of driving their initial establishment (i.e., make synapses). Since few SAMs were identified that mediate initial synapse formation, it is difficult to develop methods that enable experimental control of synaptic connections by targeted expression of these SAMs. To overcome this difficulty, we engineered novel SAMs from bacterial proteins with no eukaryotic homologues that drive synapse formation. We named these engineered adhesion proteins “Barnoligin” and “Starexin” because they were assembled from parts of Barnase and Neuroligin-1 or of Barstar and Neurexin3β, respectively. Barnoligin and Starexin robustly induce the formation of synaptic specializations in a specific and directional manner in cultured neurons. Synapse formation by Barnoligin and Starexin requires both their extracellular Barnase- and Barstar-derived interaction domains and their Neuroligin- and Neurexin-derived intracellular signaling domains. Our findings support a model of synapse formation whereby trans-synaptic interactions by SAMs drive synapse organization via adhesive interactions that activate signaling cascades. |
format | Online Article Text |
id | pubmed-9934208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-99342082023-02-17 Engineered adhesion molecules drive synapse organization Hale, W. Dylan Südhof, Thomas C. Huganir, Richard L. Proc Natl Acad Sci U S A Biological Sciences In multicellular organisms, cell-adhesion molecules connect cells into tissues and mediate intercellular signaling between these cells. In vertebrate brains, synaptic cell-adhesion molecules (SAMs) guide the formation, specification, and plasticity of synapses. Some SAMs, when overexpressed in cultured neurons or in heterologous cells co-cultured with neurons, drive formation of synaptic specializations onto the overexpressing cells. However, genetic deletion of the same SAMs from neurons often has no effect on synapse numbers, but frequently severely impairs synaptic transmission, suggesting that most SAMs control the function and plasticity of synapses (i.e., organize synapses) instead of driving their initial establishment (i.e., make synapses). Since few SAMs were identified that mediate initial synapse formation, it is difficult to develop methods that enable experimental control of synaptic connections by targeted expression of these SAMs. To overcome this difficulty, we engineered novel SAMs from bacterial proteins with no eukaryotic homologues that drive synapse formation. We named these engineered adhesion proteins “Barnoligin” and “Starexin” because they were assembled from parts of Barnase and Neuroligin-1 or of Barstar and Neurexin3β, respectively. Barnoligin and Starexin robustly induce the formation of synaptic specializations in a specific and directional manner in cultured neurons. Synapse formation by Barnoligin and Starexin requires both their extracellular Barnase- and Barstar-derived interaction domains and their Neuroligin- and Neurexin-derived intracellular signaling domains. Our findings support a model of synapse formation whereby trans-synaptic interactions by SAMs drive synapse organization via adhesive interactions that activate signaling cascades. National Academy of Sciences 2023-01-13 2023-01-17 /pmc/articles/PMC9934208/ /pubmed/36638214 http://dx.doi.org/10.1073/pnas.2215905120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Biological Sciences Hale, W. Dylan Südhof, Thomas C. Huganir, Richard L. Engineered adhesion molecules drive synapse organization |
title | Engineered adhesion molecules drive synapse organization |
title_full | Engineered adhesion molecules drive synapse organization |
title_fullStr | Engineered adhesion molecules drive synapse organization |
title_full_unstemmed | Engineered adhesion molecules drive synapse organization |
title_short | Engineered adhesion molecules drive synapse organization |
title_sort | engineered adhesion molecules drive synapse organization |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934208/ https://www.ncbi.nlm.nih.gov/pubmed/36638214 http://dx.doi.org/10.1073/pnas.2215905120 |
work_keys_str_mv | AT halewdylan engineeredadhesionmoleculesdrivesynapseorganization AT sudhofthomasc engineeredadhesionmoleculesdrivesynapseorganization AT huganirrichardl engineeredadhesionmoleculesdrivesynapseorganization |