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

Abstract 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...

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Autores principales: Qi Shi, Yingying Ge, Wanxia He, Xiangyou Hu, Riqiang Yan
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/3bf3b7894f934f8b9509ab236b90f025
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spelling oai:doaj.org-article:3bf3b7894f934f8b9509ab236b90f0252021-12-02T15:04:56ZRTN1 and RTN3 protein are differentially associated with senile plaques in Alzheimer’s brains10.1038/s41598-017-05504-92045-2322https://doaj.org/article/3bf3b7894f934f8b9509ab236b90f0252017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05504-9https://doaj.org/toc/2045-2322Abstract 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.Qi ShiYingying GeWanxia HeXiangyou HuRiqiang YanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Qi Shi
Yingying Ge
Wanxia He
Xiangyou Hu
Riqiang Yan
RTN1 and RTN3 protein are differentially associated with senile plaques in Alzheimer’s brains
description Abstract 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.
format article
author Qi Shi
Yingying Ge
Wanxia He
Xiangyou Hu
Riqiang Yan
author_facet Qi Shi
Yingying Ge
Wanxia He
Xiangyou Hu
Riqiang Yan
author_sort Qi Shi
title 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_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_sort rtn1 and rtn3 protein are differentially associated with senile plaques in alzheimer’s brains
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/3bf3b7894f934f8b9509ab236b90f025
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