An important role of PHRF1 in dendritic architecture and memory formation by modulating TGF-β signaling

Abstract PHRF1 is involved in transforming growth factor β (TGF-β) signaling to constrain the formation of acute promyelocytic leukemia (APL) in mouse APL models. PHRF1 also participates in modulating non-homologous end-joining. However, the role of PHRF1 in mammalian dendrite architecture and synap...

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Autores principales: Ting-Wei Shih, Li-Jen Lee, Ho-Ching Chang, Hung-Wei Lin, Mau-Sun Chang
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Publicado: Nature Portfolio 2020
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Acceso en línea:https://doaj.org/article/e3f25b96401d48c68aa70b8efa268aab
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spelling oai:doaj.org-article:e3f25b96401d48c68aa70b8efa268aab2021-12-02T16:32:12ZAn important role of PHRF1 in dendritic architecture and memory formation by modulating TGF-β signaling10.1038/s41598-020-67675-22045-2322https://doaj.org/article/e3f25b96401d48c68aa70b8efa268aab2020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-67675-2https://doaj.org/toc/2045-2322Abstract PHRF1 is involved in transforming growth factor β (TGF-β) signaling to constrain the formation of acute promyelocytic leukemia (APL) in mouse APL models. PHRF1 also participates in modulating non-homologous end-joining. However, the role of PHRF1 in mammalian dendrite architecture and synaptic plasticity is unclear. Here, we investigated the role of PHRF1 in dendritic formation in the murine hippocampus using Camk2a promoter driven-iCre recombinase to conduct a PHRF1 conditional knockout, namely PHRF1Δ/Δ, in the forebrain region. PHRF1Δ/Δ mice developed normally, but exhibited anxiety-like behaviors and displayed defective spatial memory. Alterations of dendritic complexity in apical and basal dendrites of pyramidal neurons were noticed in PHRF1Δ/Δ mutants. Furthermore, electrical stimulation in the hippocampal CA1 region after the TGF-β1 treatment showed a reduced synaptic plasticity in PHRF1Δ/Δ mice. Immunoblotting analysis indicated that PHRF1 ablation affected the TGF-β signaling. Collectively, our results demonstrate that PHRF1 is important for the dendritic architecture and required for spatial memory formation in the hippocampus.Ting-Wei ShihLi-Jen LeeHo-Ching ChangHung-Wei LinMau-Sun ChangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ting-Wei Shih
Li-Jen Lee
Ho-Ching Chang
Hung-Wei Lin
Mau-Sun Chang
An important role of PHRF1 in dendritic architecture and memory formation by modulating TGF-β signaling
description Abstract PHRF1 is involved in transforming growth factor β (TGF-β) signaling to constrain the formation of acute promyelocytic leukemia (APL) in mouse APL models. PHRF1 also participates in modulating non-homologous end-joining. However, the role of PHRF1 in mammalian dendrite architecture and synaptic plasticity is unclear. Here, we investigated the role of PHRF1 in dendritic formation in the murine hippocampus using Camk2a promoter driven-iCre recombinase to conduct a PHRF1 conditional knockout, namely PHRF1Δ/Δ, in the forebrain region. PHRF1Δ/Δ mice developed normally, but exhibited anxiety-like behaviors and displayed defective spatial memory. Alterations of dendritic complexity in apical and basal dendrites of pyramidal neurons were noticed in PHRF1Δ/Δ mutants. Furthermore, electrical stimulation in the hippocampal CA1 region after the TGF-β1 treatment showed a reduced synaptic plasticity in PHRF1Δ/Δ mice. Immunoblotting analysis indicated that PHRF1 ablation affected the TGF-β signaling. Collectively, our results demonstrate that PHRF1 is important for the dendritic architecture and required for spatial memory formation in the hippocampus.
format article
author Ting-Wei Shih
Li-Jen Lee
Ho-Ching Chang
Hung-Wei Lin
Mau-Sun Chang
author_facet Ting-Wei Shih
Li-Jen Lee
Ho-Ching Chang
Hung-Wei Lin
Mau-Sun Chang
author_sort Ting-Wei Shih
title An important role of PHRF1 in dendritic architecture and memory formation by modulating TGF-β signaling
title_short An important role of PHRF1 in dendritic architecture and memory formation by modulating TGF-β signaling
title_full An important role of PHRF1 in dendritic architecture and memory formation by modulating TGF-β signaling
title_fullStr An important role of PHRF1 in dendritic architecture and memory formation by modulating TGF-β signaling
title_full_unstemmed An important role of PHRF1 in dendritic architecture and memory formation by modulating TGF-β signaling
title_sort important role of phrf1 in dendritic architecture and memory formation by modulating tgf-β signaling
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/e3f25b96401d48c68aa70b8efa268aab
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