Cargando…

Live-Cell Imaging of Single Neurotrophin Receptor Molecules on Human Neurons in Alzheimer’s Disease

Neurotrophin receptors such as the tropomyosin receptor kinase A receptor (TrkA) and the low-affinity binding p75 neurotrophin receptor p75(NTR) play a critical role in neuronal survival and their functions are altered in Alzheimer’s disease (AD). Changes in the dynamics of receptors on the plasma m...

Descripción completa

Detalles Bibliográficos
Autores principales: Barabás, Klaudia, Kobolák, Julianna, Godó, Soma, Kovács, Tamás, Ernszt, Dávid, Kecskés, Miklós, Varga, Csaba, Jánosi, Tibor Z., Fujiwara, Takahiro, Kusumi, Akihiro, Téglási, Annamária, Dinnyés, András, Ábrahám, István M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708879/
https://www.ncbi.nlm.nih.gov/pubmed/34948057
http://dx.doi.org/10.3390/ijms222413260
_version_ 1784622796253429760
author Barabás, Klaudia
Kobolák, Julianna
Godó, Soma
Kovács, Tamás
Ernszt, Dávid
Kecskés, Miklós
Varga, Csaba
Jánosi, Tibor Z.
Fujiwara, Takahiro
Kusumi, Akihiro
Téglási, Annamária
Dinnyés, András
Ábrahám, István M.
author_facet Barabás, Klaudia
Kobolák, Julianna
Godó, Soma
Kovács, Tamás
Ernszt, Dávid
Kecskés, Miklós
Varga, Csaba
Jánosi, Tibor Z.
Fujiwara, Takahiro
Kusumi, Akihiro
Téglási, Annamária
Dinnyés, András
Ábrahám, István M.
author_sort Barabás, Klaudia
collection PubMed
description Neurotrophin receptors such as the tropomyosin receptor kinase A receptor (TrkA) and the low-affinity binding p75 neurotrophin receptor p75(NTR) play a critical role in neuronal survival and their functions are altered in Alzheimer’s disease (AD). Changes in the dynamics of receptors on the plasma membrane are essential to receptor function. However, whether receptor dynamics are affected in different pathophysiological conditions is unexplored. Using live-cell single-molecule imaging, we examined the surface trafficking of TrkA and p75(NTR) molecules on live neurons that were derived from human-induced pluripotent stem cells (hiPSCs) of presenilin 1 (PSEN1) mutant familial AD (fAD) patients and non-demented control subjects. Our results show that the surface movement of TrkA and p75(NTR) and the activation of TrkA- and p75(NTR)-related phosphoinositide-3-kinase (PI3K)/serine/threonine-protein kinase (AKT) signaling pathways are altered in neurons that are derived from patients suffering from fAD compared to controls. These results provide evidence for altered surface movement of receptors in AD and highlight the importance of investigating receptor dynamics in disease conditions. Uncovering these mechanisms might enable novel therapies for AD.
format Online
Article
Text
id pubmed-8708879
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-87088792021-12-25 Live-Cell Imaging of Single Neurotrophin Receptor Molecules on Human Neurons in Alzheimer’s Disease Barabás, Klaudia Kobolák, Julianna Godó, Soma Kovács, Tamás Ernszt, Dávid Kecskés, Miklós Varga, Csaba Jánosi, Tibor Z. Fujiwara, Takahiro Kusumi, Akihiro Téglási, Annamária Dinnyés, András Ábrahám, István M. Int J Mol Sci Article Neurotrophin receptors such as the tropomyosin receptor kinase A receptor (TrkA) and the low-affinity binding p75 neurotrophin receptor p75(NTR) play a critical role in neuronal survival and their functions are altered in Alzheimer’s disease (AD). Changes in the dynamics of receptors on the plasma membrane are essential to receptor function. However, whether receptor dynamics are affected in different pathophysiological conditions is unexplored. Using live-cell single-molecule imaging, we examined the surface trafficking of TrkA and p75(NTR) molecules on live neurons that were derived from human-induced pluripotent stem cells (hiPSCs) of presenilin 1 (PSEN1) mutant familial AD (fAD) patients and non-demented control subjects. Our results show that the surface movement of TrkA and p75(NTR) and the activation of TrkA- and p75(NTR)-related phosphoinositide-3-kinase (PI3K)/serine/threonine-protein kinase (AKT) signaling pathways are altered in neurons that are derived from patients suffering from fAD compared to controls. These results provide evidence for altered surface movement of receptors in AD and highlight the importance of investigating receptor dynamics in disease conditions. Uncovering these mechanisms might enable novel therapies for AD. MDPI 2021-12-09 /pmc/articles/PMC8708879/ /pubmed/34948057 http://dx.doi.org/10.3390/ijms222413260 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Barabás, Klaudia
Kobolák, Julianna
Godó, Soma
Kovács, Tamás
Ernszt, Dávid
Kecskés, Miklós
Varga, Csaba
Jánosi, Tibor Z.
Fujiwara, Takahiro
Kusumi, Akihiro
Téglási, Annamária
Dinnyés, András
Ábrahám, István M.
Live-Cell Imaging of Single Neurotrophin Receptor Molecules on Human Neurons in Alzheimer’s Disease
title Live-Cell Imaging of Single Neurotrophin Receptor Molecules on Human Neurons in Alzheimer’s Disease
title_full Live-Cell Imaging of Single Neurotrophin Receptor Molecules on Human Neurons in Alzheimer’s Disease
title_fullStr Live-Cell Imaging of Single Neurotrophin Receptor Molecules on Human Neurons in Alzheimer’s Disease
title_full_unstemmed Live-Cell Imaging of Single Neurotrophin Receptor Molecules on Human Neurons in Alzheimer’s Disease
title_short Live-Cell Imaging of Single Neurotrophin Receptor Molecules on Human Neurons in Alzheimer’s Disease
title_sort live-cell imaging of single neurotrophin receptor molecules on human neurons in alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708879/
https://www.ncbi.nlm.nih.gov/pubmed/34948057
http://dx.doi.org/10.3390/ijms222413260
work_keys_str_mv AT barabasklaudia livecellimagingofsingleneurotrophinreceptormoleculesonhumanneuronsinalzheimersdisease
AT kobolakjulianna livecellimagingofsingleneurotrophinreceptormoleculesonhumanneuronsinalzheimersdisease
AT godosoma livecellimagingofsingleneurotrophinreceptormoleculesonhumanneuronsinalzheimersdisease
AT kovacstamas livecellimagingofsingleneurotrophinreceptormoleculesonhumanneuronsinalzheimersdisease
AT ernsztdavid livecellimagingofsingleneurotrophinreceptormoleculesonhumanneuronsinalzheimersdisease
AT kecskesmiklos livecellimagingofsingleneurotrophinreceptormoleculesonhumanneuronsinalzheimersdisease
AT vargacsaba livecellimagingofsingleneurotrophinreceptormoleculesonhumanneuronsinalzheimersdisease
AT janositiborz livecellimagingofsingleneurotrophinreceptormoleculesonhumanneuronsinalzheimersdisease
AT fujiwaratakahiro livecellimagingofsingleneurotrophinreceptormoleculesonhumanneuronsinalzheimersdisease
AT kusumiakihiro livecellimagingofsingleneurotrophinreceptormoleculesonhumanneuronsinalzheimersdisease
AT teglasiannamaria livecellimagingofsingleneurotrophinreceptormoleculesonhumanneuronsinalzheimersdisease
AT dinnyesandras livecellimagingofsingleneurotrophinreceptormoleculesonhumanneuronsinalzheimersdisease
AT abrahamistvanm livecellimagingofsingleneurotrophinreceptormoleculesonhumanneuronsinalzheimersdisease