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Endosome and Lysosome Membrane Properties Functionally Link to γ-Secretase in Live/Intact Cells
Our unique multiplexed imaging assays employing FRET biosensors have previously detected that γ-secretase processes APP C99 primarily in late endosomes and lysosomes in live/intact neurons. Moreover we have shown that Aβ peptides are enriched in the same subcellular loci. Given that γ-secretase is i...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10007619/ https://www.ncbi.nlm.nih.gov/pubmed/36904854 http://dx.doi.org/10.3390/s23052651 |
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author | Houser, Mei C. Q. Mitchell, Shane P. C. Sinha, Priyanka Lundin, Brianna Berezovska, Oksana Maesako, Masato |
author_facet | Houser, Mei C. Q. Mitchell, Shane P. C. Sinha, Priyanka Lundin, Brianna Berezovska, Oksana Maesako, Masato |
author_sort | Houser, Mei C. Q. |
collection | PubMed |
description | Our unique multiplexed imaging assays employing FRET biosensors have previously detected that γ-secretase processes APP C99 primarily in late endosomes and lysosomes in live/intact neurons. Moreover we have shown that Aβ peptides are enriched in the same subcellular loci. Given that γ-secretase is integrated into the membrane bilayer and functionally links to lipid membrane properties in vitro, it is presumable that γ-secretase function correlates with endosome and lysosome membrane properties in live/intact cells. In the present study, we show using unique live-cell imaging and biochemical assays that the endo-lysosomal membrane in primary neurons is more disordered and, as a result, more permeable than in CHO cells. Interestingly, γ-secretase processivity is decreased in primary neurons, resulting in the predominant production of long Aβ42 instead of short Aβ38. In contrast, CHO cells favor Aβ38 over the Aβ42 generation. Our findings are consistent with the previous in vitro studies, demonstrating the functional interaction between lipid membrane properties and γ-secretase and provide further evidence that γ-secretase acts in late endosomes and lysosomes in live/intact cells. |
format | Online Article Text |
id | pubmed-10007619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100076192023-03-12 Endosome and Lysosome Membrane Properties Functionally Link to γ-Secretase in Live/Intact Cells Houser, Mei C. Q. Mitchell, Shane P. C. Sinha, Priyanka Lundin, Brianna Berezovska, Oksana Maesako, Masato Sensors (Basel) Article Our unique multiplexed imaging assays employing FRET biosensors have previously detected that γ-secretase processes APP C99 primarily in late endosomes and lysosomes in live/intact neurons. Moreover we have shown that Aβ peptides are enriched in the same subcellular loci. Given that γ-secretase is integrated into the membrane bilayer and functionally links to lipid membrane properties in vitro, it is presumable that γ-secretase function correlates with endosome and lysosome membrane properties in live/intact cells. In the present study, we show using unique live-cell imaging and biochemical assays that the endo-lysosomal membrane in primary neurons is more disordered and, as a result, more permeable than in CHO cells. Interestingly, γ-secretase processivity is decreased in primary neurons, resulting in the predominant production of long Aβ42 instead of short Aβ38. In contrast, CHO cells favor Aβ38 over the Aβ42 generation. Our findings are consistent with the previous in vitro studies, demonstrating the functional interaction between lipid membrane properties and γ-secretase and provide further evidence that γ-secretase acts in late endosomes and lysosomes in live/intact cells. MDPI 2023-02-28 /pmc/articles/PMC10007619/ /pubmed/36904854 http://dx.doi.org/10.3390/s23052651 Text en © 2023 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 Houser, Mei C. Q. Mitchell, Shane P. C. Sinha, Priyanka Lundin, Brianna Berezovska, Oksana Maesako, Masato Endosome and Lysosome Membrane Properties Functionally Link to γ-Secretase in Live/Intact Cells |
title | Endosome and Lysosome Membrane Properties Functionally Link to γ-Secretase in Live/Intact Cells |
title_full | Endosome and Lysosome Membrane Properties Functionally Link to γ-Secretase in Live/Intact Cells |
title_fullStr | Endosome and Lysosome Membrane Properties Functionally Link to γ-Secretase in Live/Intact Cells |
title_full_unstemmed | Endosome and Lysosome Membrane Properties Functionally Link to γ-Secretase in Live/Intact Cells |
title_short | Endosome and Lysosome Membrane Properties Functionally Link to γ-Secretase in Live/Intact Cells |
title_sort | endosome and lysosome membrane properties functionally link to γ-secretase in live/intact cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10007619/ https://www.ncbi.nlm.nih.gov/pubmed/36904854 http://dx.doi.org/10.3390/s23052651 |
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