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An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with age
Micropeptides, encoded from small open reading frames of 300 nucleotides or less, are hidden throughout mammalian genomes, though few functional studies of micropeptides in the brain are published. Here, we describe a micropeptide known as the Plasticity–Associated Neural Transcript Short (Pants), l...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246188/ https://www.ncbi.nlm.nih.gov/pubmed/35771867 http://dx.doi.org/10.1371/journal.pone.0269404 |
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author | Kragness, S. Clark, Z. Mullin, A. Guidry, J. Earls, L. R. |
author_facet | Kragness, S. Clark, Z. Mullin, A. Guidry, J. Earls, L. R. |
author_sort | Kragness, S. |
collection | PubMed |
description | Micropeptides, encoded from small open reading frames of 300 nucleotides or less, are hidden throughout mammalian genomes, though few functional studies of micropeptides in the brain are published. Here, we describe a micropeptide known as the Plasticity–Associated Neural Transcript Short (Pants), located in the 22q11.2 region of the human genome, the microdeletion of which conveys a high risk for schizophrenia. Our data show that Pants is upregulated in early adulthood in the mossy fiber circuit of the hippocampus, where it exerts a powerful negative effect on long-term potentiation (LTP). Further, we find that Pants is secreted from neurons, where it associates with synapses but is rapidly degraded with stimulation. Pants dynamically interacts with Rtn4/Nogo-A, a well-studied regulator of adult plasticity. Pants interaction with Nogo-A augments its influence over postsynaptic AMPA receptor clustering, thus gating plasticity at adult synapses. This work shows that neural micropeptides can act as architectural modules that increase the functional diversity of the known proteome. |
format | Online Article Text |
id | pubmed-9246188 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-92461882022-07-01 An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with age Kragness, S. Clark, Z. Mullin, A. Guidry, J. Earls, L. R. PLoS One Research Article Micropeptides, encoded from small open reading frames of 300 nucleotides or less, are hidden throughout mammalian genomes, though few functional studies of micropeptides in the brain are published. Here, we describe a micropeptide known as the Plasticity–Associated Neural Transcript Short (Pants), located in the 22q11.2 region of the human genome, the microdeletion of which conveys a high risk for schizophrenia. Our data show that Pants is upregulated in early adulthood in the mossy fiber circuit of the hippocampus, where it exerts a powerful negative effect on long-term potentiation (LTP). Further, we find that Pants is secreted from neurons, where it associates with synapses but is rapidly degraded with stimulation. Pants dynamically interacts with Rtn4/Nogo-A, a well-studied regulator of adult plasticity. Pants interaction with Nogo-A augments its influence over postsynaptic AMPA receptor clustering, thus gating plasticity at adult synapses. This work shows that neural micropeptides can act as architectural modules that increase the functional diversity of the known proteome. Public Library of Science 2022-06-30 /pmc/articles/PMC9246188/ /pubmed/35771867 http://dx.doi.org/10.1371/journal.pone.0269404 Text en © 2022 Kragness et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Kragness, S. Clark, Z. Mullin, A. Guidry, J. Earls, L. R. An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with age |
title | An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with age |
title_full | An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with age |
title_fullStr | An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with age |
title_full_unstemmed | An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with age |
title_short | An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with age |
title_sort | rtn4/nogo-a-interacting micropeptide modulates synaptic plasticity with age |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246188/ https://www.ncbi.nlm.nih.gov/pubmed/35771867 http://dx.doi.org/10.1371/journal.pone.0269404 |
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