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Amyloid Beta Is Internalized via Macropinocytosis, an HSPG- and Lipid Raft-Dependent and Rac1-Mediated Process
Intracellular amyloid β peptide (Aβ) accumulation has drawn attention in relation to the pathophysiology of Alzheimer’s disease in addition to its extracellular deposition as senile plaque. Cellular uptake of extracellular Aβ is one of the possible mechanisms by which intracellular Aβ deposits form....
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524458/ https://www.ncbi.nlm.nih.gov/pubmed/36187354 http://dx.doi.org/10.3389/fnmol.2022.804702 |
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author | Nazere, Keyoumu Takahashi, Tetsuya Hara, Naoyuki Muguruma, Kazuki Nakamori, Masahiro Yamazaki, Yu Morino, Hiroyuki Maruyama, Hirofumi |
author_facet | Nazere, Keyoumu Takahashi, Tetsuya Hara, Naoyuki Muguruma, Kazuki Nakamori, Masahiro Yamazaki, Yu Morino, Hiroyuki Maruyama, Hirofumi |
author_sort | Nazere, Keyoumu |
collection | PubMed |
description | Intracellular amyloid β peptide (Aβ) accumulation has drawn attention in relation to the pathophysiology of Alzheimer’s disease in addition to its extracellular deposition as senile plaque. Cellular uptake of extracellular Aβ is one of the possible mechanisms by which intracellular Aβ deposits form. Given the relevance of Aβ inside cells, it is important to understand the mechanism by which it is taken up by them. In this study, we elucidated that Neuro2A and SH-SY5Y cells internalize specifically oligomerized Aβ in a time- and dose-dependent manner. The depletion of plasma membrane cholesterol with methyl-β-cyclodextrin or treatment with trypsin diminished the internalization of oAβ, suggesting that the oAβ uptake might be both a lipid raft-dependent and heparan sulfate proteoglycan-mediated process. Treatment with a macropinocytosis inhibitor (ethylisopropyl amiloride and wortmannin) also drastically reduced the uptake of oligomer-Aβ (oAβ). oAβ-treated cells exhibited an increase in Rac1 activity, indicating that macropinocytosis induced by oAβ is regulated by these small GTPases. These findings suggest that macropinocytosis is a major endocytic route through which oAβ42 enters cells. |
format | Online Article Text |
id | pubmed-9524458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95244582022-10-01 Amyloid Beta Is Internalized via Macropinocytosis, an HSPG- and Lipid Raft-Dependent and Rac1-Mediated Process Nazere, Keyoumu Takahashi, Tetsuya Hara, Naoyuki Muguruma, Kazuki Nakamori, Masahiro Yamazaki, Yu Morino, Hiroyuki Maruyama, Hirofumi Front Mol Neurosci Molecular Neuroscience Intracellular amyloid β peptide (Aβ) accumulation has drawn attention in relation to the pathophysiology of Alzheimer’s disease in addition to its extracellular deposition as senile plaque. Cellular uptake of extracellular Aβ is one of the possible mechanisms by which intracellular Aβ deposits form. Given the relevance of Aβ inside cells, it is important to understand the mechanism by which it is taken up by them. In this study, we elucidated that Neuro2A and SH-SY5Y cells internalize specifically oligomerized Aβ in a time- and dose-dependent manner. The depletion of plasma membrane cholesterol with methyl-β-cyclodextrin or treatment with trypsin diminished the internalization of oAβ, suggesting that the oAβ uptake might be both a lipid raft-dependent and heparan sulfate proteoglycan-mediated process. Treatment with a macropinocytosis inhibitor (ethylisopropyl amiloride and wortmannin) also drastically reduced the uptake of oligomer-Aβ (oAβ). oAβ-treated cells exhibited an increase in Rac1 activity, indicating that macropinocytosis induced by oAβ is regulated by these small GTPases. These findings suggest that macropinocytosis is a major endocytic route through which oAβ42 enters cells. Frontiers Media S.A. 2022-02-11 /pmc/articles/PMC9524458/ /pubmed/36187354 http://dx.doi.org/10.3389/fnmol.2022.804702 Text en Copyright © 2022 Nazere, Takahashi, Hara, Muguruma, Nakamori, Yamazaki, Morino and Maruyama. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Neuroscience Nazere, Keyoumu Takahashi, Tetsuya Hara, Naoyuki Muguruma, Kazuki Nakamori, Masahiro Yamazaki, Yu Morino, Hiroyuki Maruyama, Hirofumi Amyloid Beta Is Internalized via Macropinocytosis, an HSPG- and Lipid Raft-Dependent and Rac1-Mediated Process |
title | Amyloid Beta Is Internalized via Macropinocytosis, an HSPG- and Lipid Raft-Dependent and Rac1-Mediated Process |
title_full | Amyloid Beta Is Internalized via Macropinocytosis, an HSPG- and Lipid Raft-Dependent and Rac1-Mediated Process |
title_fullStr | Amyloid Beta Is Internalized via Macropinocytosis, an HSPG- and Lipid Raft-Dependent and Rac1-Mediated Process |
title_full_unstemmed | Amyloid Beta Is Internalized via Macropinocytosis, an HSPG- and Lipid Raft-Dependent and Rac1-Mediated Process |
title_short | Amyloid Beta Is Internalized via Macropinocytosis, an HSPG- and Lipid Raft-Dependent and Rac1-Mediated Process |
title_sort | amyloid beta is internalized via macropinocytosis, an hspg- and lipid raft-dependent and rac1-mediated process |
topic | Molecular Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524458/ https://www.ncbi.nlm.nih.gov/pubmed/36187354 http://dx.doi.org/10.3389/fnmol.2022.804702 |
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