Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia
Cultured mouse peritoneal macrophages release large numbers of ~30-nm cholesterol-rich particles. Here, we show that those particles represent fragments of the plasma membrane that are pulled away and left behind during the projection and retraction of filopodia and lamellipodia. Consistent with thi...
| 出版年: | eLife |
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| 主要な著者: | , , , , , , , , , , , |
| フォーマット: | 論文 |
| 言語: | 英語 |
| 出版事項: |
eLife Sciences Publications Ltd
2019-09-01
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| 主題: | |
| オンライン･アクセス: | https://elifesciences.org/articles/50231 |
| _version_ | 1852645247787466752 |
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| author | Xuchen Hu Thomas A Weston Cuiwen He Rachel S Jung Patrick J Heizer Brian D Young Yiping Tu Peter Tontonoz James A Wohlschlegel Haibo Jiang Stephen G Young Loren G Fong |
| author_facet | Xuchen Hu Thomas A Weston Cuiwen He Rachel S Jung Patrick J Heizer Brian D Young Yiping Tu Peter Tontonoz James A Wohlschlegel Haibo Jiang Stephen G Young Loren G Fong |
| author_sort | Xuchen Hu |
| collection | DOAJ |
| container_title | eLife |
| description | Cultured mouse peritoneal macrophages release large numbers of ~30-nm cholesterol-rich particles. Here, we show that those particles represent fragments of the plasma membrane that are pulled away and left behind during the projection and retraction of filopodia and lamellipodia. Consistent with this finding, the particles are enriched in proteins found in focal adhesions, which attach macrophages to the substrate. The release of particles is abolished by blocking cell movement (either by depolymerizing actin with latrunculin A or by inhibiting myosin II with blebbistatin). Confocal microscopy and NanoSIMS imaging studies revealed that the plasma membrane–derived particles are enriched in ‘accessible cholesterol’ (a mobile pool of cholesterol detectable with the modified cytolysin ALO-D4) but not in sphingolipid-sequestered cholesterol [a pool detectable with ostreolysin A (OlyA)]. The discovery that macrophages release cholesterol-rich particles during cellular locomotion is likely relevant to cholesterol efflux and could contribute to extracellular cholesterol deposition in atherosclerotic plaques. |
| format | Article |
| id | doaj-art-c8058d365a7d44e2aede24f03b4dacae |
| institution | Directory of Open Access Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2019-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| spelling | doaj-art-c8058d365a7d44e2aede24f03b4dacae2025-08-19T21:43:13ZengeLife Sciences Publications LtdeLife2050-084X2019-09-01810.7554/eLife.50231Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodiaXuchen Hu0https://orcid.org/0000-0002-0944-624XThomas A Weston1Cuiwen He2Rachel S Jung3Patrick J Heizer4Brian D Young5Yiping Tu6Peter Tontonoz7https://orcid.org/0000-0003-1259-0477James A Wohlschlegel8Haibo Jiang9https://orcid.org/0000-0002-2384-4826Stephen G Young10https://orcid.org/0000-0001-7270-3176Loren G Fong11https://orcid.org/0000-0002-4465-5290Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Biological Chemistry, University of California, Los Angeles, Los Angeles, United StatesDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Biological Chemistry, University of California, Los Angeles, Los Angeles, United StatesDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; School of Molecular Sciences, University of Western Australia, Perth, AustraliaDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesCultured mouse peritoneal macrophages release large numbers of ~30-nm cholesterol-rich particles. Here, we show that those particles represent fragments of the plasma membrane that are pulled away and left behind during the projection and retraction of filopodia and lamellipodia. Consistent with this finding, the particles are enriched in proteins found in focal adhesions, which attach macrophages to the substrate. The release of particles is abolished by blocking cell movement (either by depolymerizing actin with latrunculin A or by inhibiting myosin II with blebbistatin). Confocal microscopy and NanoSIMS imaging studies revealed that the plasma membrane–derived particles are enriched in ‘accessible cholesterol’ (a mobile pool of cholesterol detectable with the modified cytolysin ALO-D4) but not in sphingolipid-sequestered cholesterol [a pool detectable with ostreolysin A (OlyA)]. The discovery that macrophages release cholesterol-rich particles during cellular locomotion is likely relevant to cholesterol efflux and could contribute to extracellular cholesterol deposition in atherosclerotic plaques.https://elifesciences.org/articles/50231accessible cholesterolNanoSIMSfocal adhesionscholesterol efflux |
| spellingShingle | Xuchen Hu Thomas A Weston Cuiwen He Rachel S Jung Patrick J Heizer Brian D Young Yiping Tu Peter Tontonoz James A Wohlschlegel Haibo Jiang Stephen G Young Loren G Fong Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia accessible cholesterol NanoSIMS focal adhesions cholesterol efflux |
| title | Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia |
| title_full | Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia |
| title_fullStr | Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia |
| title_full_unstemmed | Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia |
| title_short | Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia |
| title_sort | release of cholesterol rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia |
| topic | accessible cholesterol NanoSIMS focal adhesions cholesterol efflux |
| url | https://elifesciences.org/articles/50231 |
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