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RTN1 and RTN3 protein are differentially associated with senile plaques in Alzheimer’s brains

Reticulon proteins (RTNs), consisting of RTN1 to RTN4, were previously shown to interact with BACE1 by negatively modulating its secretase activity. In RTN3-null mice, RTN1 expression was slightly elevated. To understand the in vivo role of RTN1, we generated RTN1-null mice and compared the effects...

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Autores principales: Shi, Qi, Ge, Yingying, He, Wanxia, Hu, Xiangyou, Yan, Riqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522448/
https://www.ncbi.nlm.nih.gov/pubmed/28733667
http://dx.doi.org/10.1038/s41598-017-05504-9
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author Shi, Qi
Ge, Yingying
He, Wanxia
Hu, Xiangyou
Yan, Riqiang
author_facet Shi, Qi
Ge, Yingying
He, Wanxia
Hu, Xiangyou
Yan, Riqiang
author_sort Shi, Qi
collection PubMed
description Reticulon proteins (RTNs), consisting of RTN1 to RTN4, were previously shown to interact with BACE1 by negatively modulating its secretase activity. In RTN3-null mice, RTN1 expression was slightly elevated. To understand the in vivo role of RTN1, we generated RTN1-null mice and compared the effects of RTN1 and RTN3 on BACE1 modulation. We show that RTN1 is mostly expressed by neurons and not by glial cells under normal conditions, similar to the expression of RTN3. However, RTN1 is more localized in dendrites and is an excellent marker for dendrites of Purkinje cells, while RTN3 expression is less evident in dendrites. This differential localization also correlates with their associations with amyloid plaques in Alzheimer’s brains: RTN3, but not RTN1, is abundantly enriched in dystrophic neurites. RTN3 deficiency causes elevation of BACE1 protein levels, while RTN1 deficiency shows no obvious effects on BACE1 activity due to compensation by RTN3, as RTN1 deficiency causes elevation of RTN3 expression. Hence, expression of RTN1 and RTN3 is tightly regulated in mouse brains. Together, our data show that RTN1 and RTN3 have differential effects on the formation of senile plaques in Alzheimer’s brains and that RTN3 has a more prominent role in Alzheimer’s pathogenesis.
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spelling pubmed-55224482017-07-26 RTN1 and RTN3 protein are differentially associated with senile plaques in Alzheimer’s brains Shi, Qi Ge, Yingying He, Wanxia Hu, Xiangyou Yan, Riqiang Sci Rep Article Reticulon proteins (RTNs), consisting of RTN1 to RTN4, were previously shown to interact with BACE1 by negatively modulating its secretase activity. In RTN3-null mice, RTN1 expression was slightly elevated. To understand the in vivo role of RTN1, we generated RTN1-null mice and compared the effects of RTN1 and RTN3 on BACE1 modulation. We show that RTN1 is mostly expressed by neurons and not by glial cells under normal conditions, similar to the expression of RTN3. However, RTN1 is more localized in dendrites and is an excellent marker for dendrites of Purkinje cells, while RTN3 expression is less evident in dendrites. This differential localization also correlates with their associations with amyloid plaques in Alzheimer’s brains: RTN3, but not RTN1, is abundantly enriched in dystrophic neurites. RTN3 deficiency causes elevation of BACE1 protein levels, while RTN1 deficiency shows no obvious effects on BACE1 activity due to compensation by RTN3, as RTN1 deficiency causes elevation of RTN3 expression. Hence, expression of RTN1 and RTN3 is tightly regulated in mouse brains. Together, our data show that RTN1 and RTN3 have differential effects on the formation of senile plaques in Alzheimer’s brains and that RTN3 has a more prominent role in Alzheimer’s pathogenesis. Nature Publishing Group UK 2017-07-21 /pmc/articles/PMC5522448/ /pubmed/28733667 http://dx.doi.org/10.1038/s41598-017-05504-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Shi, Qi
Ge, Yingying
He, Wanxia
Hu, Xiangyou
Yan, Riqiang
RTN1 and RTN3 protein are differentially associated with senile plaques in Alzheimer’s brains
title RTN1 and RTN3 protein are differentially associated with senile plaques in Alzheimer’s brains
title_full RTN1 and RTN3 protein are differentially associated with senile plaques in Alzheimer’s brains
title_fullStr RTN1 and RTN3 protein are differentially associated with senile plaques in Alzheimer’s brains
title_full_unstemmed RTN1 and RTN3 protein are differentially associated with senile plaques in Alzheimer’s brains
title_short RTN1 and RTN3 protein are differentially associated with senile plaques in Alzheimer’s brains
title_sort rtn1 and rtn3 protein are differentially associated with senile plaques in alzheimer’s brains
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522448/
https://www.ncbi.nlm.nih.gov/pubmed/28733667
http://dx.doi.org/10.1038/s41598-017-05504-9
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