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Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons
Nodding syndrome is a pediatric epilepsy disorder associated with Onchocerca volvulus infection, but the mechanism driving this relationship is unclear. One hypothesis proposes that parasite-induced immune responses cross-react with human leiomodin-1 resulting in immune-mediated central nervous syst...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763904/ https://www.ncbi.nlm.nih.gov/pubmed/33321732 http://dx.doi.org/10.3390/pathogens9121036 |
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author | Nauen, David W. Haffner, Michael C. Kim, Juyun Zheng, Qizhi Yin, Hao DeMarzo, Angelo M. Mahairaki, Vasiliki Colantuoni, Carlo Pickering, J. Geoffrey Johnson, Tory P. |
author_facet | Nauen, David W. Haffner, Michael C. Kim, Juyun Zheng, Qizhi Yin, Hao DeMarzo, Angelo M. Mahairaki, Vasiliki Colantuoni, Carlo Pickering, J. Geoffrey Johnson, Tory P. |
author_sort | Nauen, David W. |
collection | PubMed |
description | Nodding syndrome is a pediatric epilepsy disorder associated with Onchocerca volvulus infection, but the mechanism driving this relationship is unclear. One hypothesis proposes that parasite-induced immune responses cross-react with human leiomodin-1 resulting in immune-mediated central nervous system (CNS) damage. However, as leiomodin-1 expression and epitope availability in human neurons remains uncharacterized, the relevance of leiomodin-1 autoimmunity is unknown. Leiomodin-1 transcript expression was assessed in silico using publicly available ribonucleic acid (RNA) sequencing databases and in tissue by in situ hybridization and quantitative polymerase chain reaction. Abundance and subcellular localization were examined by cell fractionation and immunoblotting. Leiomodin-1 transcripts were expressed in cells of the CNS, including neurons and astrocytes. Protein was detectable from all brain regions examined as well as from representative cell lines and in vitro differentiated neurons and astrocytes. Leiomodin-1 was expressed on the membrane of newly formed neurons, but not neural progenitor cells or mature neurons. Importantly, leiomodin-1 antibodies were only toxic to cells expressing leiomodin-1 on the membrane. Our findings provide evidence that leiomodin-1 is expressed in human neurons and glia. Furthermore, we show membrane expression mediates leiomodin-1 antibody toxicity, suggesting these antibodies may play a role in pathogenesis. |
format | Online Article Text |
id | pubmed-7763904 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77639042020-12-27 Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons Nauen, David W. Haffner, Michael C. Kim, Juyun Zheng, Qizhi Yin, Hao DeMarzo, Angelo M. Mahairaki, Vasiliki Colantuoni, Carlo Pickering, J. Geoffrey Johnson, Tory P. Pathogens Article Nodding syndrome is a pediatric epilepsy disorder associated with Onchocerca volvulus infection, but the mechanism driving this relationship is unclear. One hypothesis proposes that parasite-induced immune responses cross-react with human leiomodin-1 resulting in immune-mediated central nervous system (CNS) damage. However, as leiomodin-1 expression and epitope availability in human neurons remains uncharacterized, the relevance of leiomodin-1 autoimmunity is unknown. Leiomodin-1 transcript expression was assessed in silico using publicly available ribonucleic acid (RNA) sequencing databases and in tissue by in situ hybridization and quantitative polymerase chain reaction. Abundance and subcellular localization were examined by cell fractionation and immunoblotting. Leiomodin-1 transcripts were expressed in cells of the CNS, including neurons and astrocytes. Protein was detectable from all brain regions examined as well as from representative cell lines and in vitro differentiated neurons and astrocytes. Leiomodin-1 was expressed on the membrane of newly formed neurons, but not neural progenitor cells or mature neurons. Importantly, leiomodin-1 antibodies were only toxic to cells expressing leiomodin-1 on the membrane. Our findings provide evidence that leiomodin-1 is expressed in human neurons and glia. Furthermore, we show membrane expression mediates leiomodin-1 antibody toxicity, suggesting these antibodies may play a role in pathogenesis. MDPI 2020-12-10 /pmc/articles/PMC7763904/ /pubmed/33321732 http://dx.doi.org/10.3390/pathogens9121036 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nauen, David W. Haffner, Michael C. Kim, Juyun Zheng, Qizhi Yin, Hao DeMarzo, Angelo M. Mahairaki, Vasiliki Colantuoni, Carlo Pickering, J. Geoffrey Johnson, Tory P. Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons |
title | Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons |
title_full | Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons |
title_fullStr | Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons |
title_full_unstemmed | Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons |
title_short | Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons |
title_sort | putative autoantigen leiomodin-1 is expressed in the human brain and in the membrane fraction of newly formed neurons |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763904/ https://www.ncbi.nlm.nih.gov/pubmed/33321732 http://dx.doi.org/10.3390/pathogens9121036 |
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