Imaging lipid rafts reveals the principle of ApoE4-induced Aβ upregulation in human neurons
Summary: Lipid rafts in plasma membranes are thought to provide a platform for regulating signaling pathways by increasing the expression or proximity of proteins in the same pathway. Despite this understanding, the absence of direct, simultaneous observations of lipid rafts and their affiliated pro...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225001531 |
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| author | Se-In Lee Heejin Lim Na Yeon Kim Jichang Yu Joonho Cho Hyein Lee Dae Won Moon Jinsoo Seo |
| author_facet | Se-In Lee Heejin Lim Na Yeon Kim Jichang Yu Joonho Cho Hyein Lee Dae Won Moon Jinsoo Seo |
| author_sort | Se-In Lee |
| collection | DOAJ |
| description | Summary: Lipid rafts in plasma membranes are thought to provide a platform for regulating signaling pathways by increasing the expression or proximity of proteins in the same pathway. Despite this understanding, the absence of direct, simultaneous observations of lipid rafts and their affiliated proteins has hindered a comprehensive assessment of their roles across various biological contexts. Amyloid-β (Aβ), a hallmark of Alzheimer’s disease (AD), is generated from the sequential cleavage of amyloid precursor proteins (APPs) by β- and γ-secretases, primarily within endosomes after APP endocytosis by canonical clathrin-mediated endocytosis in neurons. In this study, we developed a protocol for imaging APP on lipid rafts using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and found that astrocyte ApoE4 contributes to an increase in APP localization on lipid rafts, subsequently elevating Aβ42 synthesis in a clathrin-independent manner in neurons. |
| format | Article |
| id | doaj-art-5684365d59054ff089a0a2bb01edf432 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-5684365d59054ff089a0a2bb01edf4322025-02-07T04:48:05ZengElsevieriScience2589-00422025-02-01282111893Imaging lipid rafts reveals the principle of ApoE4-induced Aβ upregulation in human neuronsSe-In Lee0Heejin Lim1Na Yeon Kim2Jichang Yu3Joonho Cho4Hyein Lee5Dae Won Moon6Jinsoo Seo7Department of Brain Sciences, Daegu Gyeongbuk Institute of Science & Technology, Daegu 42988 South KoreaDepartment of New Biology, Daegu Gyeongbuk Institute of Science & Technology, Daegu 42988 South Korea; Center for Scientific Instrumentation, Korea Basic Science Institute, Cheongju 28199 South KoreaDepartment of Brain Sciences, Daegu Gyeongbuk Institute of Science & Technology, Daegu 42988 South KoreaDepartment of Brain Sciences, Daegu Gyeongbuk Institute of Science & Technology, Daegu 42988 South KoreaDepartment of Brain Sciences, Daegu Gyeongbuk Institute of Science & Technology, Daegu 42988 South KoreaDepartment of Brain Sciences, Daegu Gyeongbuk Institute of Science & Technology, Daegu 42988 South KoreaDepartment of New Biology, Daegu Gyeongbuk Institute of Science & Technology, Daegu 42988 South Korea; Corresponding authorDepartment of Brain Sciences, Daegu Gyeongbuk Institute of Science & Technology, Daegu 42988 South Korea; Center for Synapse Diversity and Specificity, Daegu Gyeongbuk Institute of Science & Technology, Daegu 42988 South Korea; Corresponding authorSummary: Lipid rafts in plasma membranes are thought to provide a platform for regulating signaling pathways by increasing the expression or proximity of proteins in the same pathway. Despite this understanding, the absence of direct, simultaneous observations of lipid rafts and their affiliated proteins has hindered a comprehensive assessment of their roles across various biological contexts. Amyloid-β (Aβ), a hallmark of Alzheimer’s disease (AD), is generated from the sequential cleavage of amyloid precursor proteins (APPs) by β- and γ-secretases, primarily within endosomes after APP endocytosis by canonical clathrin-mediated endocytosis in neurons. In this study, we developed a protocol for imaging APP on lipid rafts using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and found that astrocyte ApoE4 contributes to an increase in APP localization on lipid rafts, subsequently elevating Aβ42 synthesis in a clathrin-independent manner in neurons.http://www.sciencedirect.com/science/article/pii/S2589004225001531Natural sciencesBiological sciencesNeuroscienceCellular neuroscienceTechniques in neuroscience |
| spellingShingle | Se-In Lee Heejin Lim Na Yeon Kim Jichang Yu Joonho Cho Hyein Lee Dae Won Moon Jinsoo Seo Imaging lipid rafts reveals the principle of ApoE4-induced Aβ upregulation in human neurons iScience Natural sciences Biological sciences Neuroscience Cellular neuroscience Techniques in neuroscience |
| title | Imaging lipid rafts reveals the principle of ApoE4-induced Aβ upregulation in human neurons |
| title_full | Imaging lipid rafts reveals the principle of ApoE4-induced Aβ upregulation in human neurons |
| title_fullStr | Imaging lipid rafts reveals the principle of ApoE4-induced Aβ upregulation in human neurons |
| title_full_unstemmed | Imaging lipid rafts reveals the principle of ApoE4-induced Aβ upregulation in human neurons |
| title_short | Imaging lipid rafts reveals the principle of ApoE4-induced Aβ upregulation in human neurons |
| title_sort | imaging lipid rafts reveals the principle of apoe4 induced aβ upregulation in human neurons |
| topic | Natural sciences Biological sciences Neuroscience Cellular neuroscience Techniques in neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225001531 |
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