Cholesterol and Sphingomyelin Polarize at the Leading Edge of Migrating Myoblasts and Involve Their Clustering in Submicrometric Domains
Myoblast migration is crucial for myogenesis and muscular tissue homeostasis. However, its spatiotemporal control remains elusive. Here, we explored the involvement of plasma membrane cholesterol and sphingolipids in this process. In resting C2C12 mouse myoblasts, those lipids clustered in sphingomy...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/2/319 |
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| author | Juliette Vanderroost Noémie Avalosse Danahe Mohammed Delia Hoffmann Patrick Henriet Christophe E. Pierreux David Alsteens Donatienne Tyteca |
| author_facet | Juliette Vanderroost Noémie Avalosse Danahe Mohammed Delia Hoffmann Patrick Henriet Christophe E. Pierreux David Alsteens Donatienne Tyteca |
| author_sort | Juliette Vanderroost |
| collection | DOAJ |
| description | Myoblast migration is crucial for myogenesis and muscular tissue homeostasis. However, its spatiotemporal control remains elusive. Here, we explored the involvement of plasma membrane cholesterol and sphingolipids in this process. In resting C2C12 mouse myoblasts, those lipids clustered in sphingomyelin/cholesterol/GM1 ganglioside (SM/chol/GM1)- and cholesterol (chol)-enriched domains, which presented a lower stiffness than the bulk membrane. Upon migration, cholesterol and sphingomyelin polarized at the front, forming cholesterol (chol)- and sphingomyelin/cholesterol (SM/chol)-enriched domains, while GM1-enriched domains polarized at the rear. A comparison of domain proportion suggested that SM/chol- and GM1-enriched domains originated from the SM/chol/GM1-coenriched domains found at resting state. Modulation of domain proportion (through cholesterol depletion, combined or not with actin polymerization inhibition, or sphingolipid synthesis inhibition) revealed that the higher the chol- and SM/chol-enriched domains, the higher the myoblast migration. At the front, chol- and SM/chol-enriched domains were found in proximity with F-actin fibers and the lateral mobility of sphingomyelin in domains was specifically restricted in a cholesterol- and cytoskeleton-dependent manner while domain abrogation impaired F-actin and focal adhesion polarization. Altogether, we showed the polarization of cholesterol and sphingomyelin and their clustering in chol- and SM/chol-enriched domains with differential properties and roles, providing a mechanism for the spatial and functional control of myoblast migration. |
| first_indexed | 2024-03-11T09:06:15Z |
| format | Article |
| id | doaj.art-b8b4704870ff44f7a5d8ce2e711d1e0b |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T09:06:15Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-b8b4704870ff44f7a5d8ce2e711d1e0b2023-11-16T19:23:30ZengMDPI AGBiomolecules2218-273X2023-02-0113231910.3390/biom13020319Cholesterol and Sphingomyelin Polarize at the Leading Edge of Migrating Myoblasts and Involve Their Clustering in Submicrometric DomainsJuliette Vanderroost0Noémie Avalosse1Danahe Mohammed2Delia Hoffmann3Patrick Henriet4Christophe E. Pierreux5David Alsteens6Donatienne Tyteca7de Duve Institute, UCLouvain, 1200 Brussels, Belgiumde Duve Institute, UCLouvain, 1200 Brussels, BelgiumLouvain Institute of Biomolecular Science and Technology (LIBST), UCLouvain, 1340 Ottignies-Louvain-la-Neuve, Belgiumde Duve Institute, UCLouvain, 1200 Brussels, Belgiumde Duve Institute, UCLouvain, 1200 Brussels, Belgiumde Duve Institute, UCLouvain, 1200 Brussels, BelgiumLouvain Institute of Biomolecular Science and Technology (LIBST), UCLouvain, 1340 Ottignies-Louvain-la-Neuve, Belgiumde Duve Institute, UCLouvain, 1200 Brussels, BelgiumMyoblast migration is crucial for myogenesis and muscular tissue homeostasis. However, its spatiotemporal control remains elusive. Here, we explored the involvement of plasma membrane cholesterol and sphingolipids in this process. In resting C2C12 mouse myoblasts, those lipids clustered in sphingomyelin/cholesterol/GM1 ganglioside (SM/chol/GM1)- and cholesterol (chol)-enriched domains, which presented a lower stiffness than the bulk membrane. Upon migration, cholesterol and sphingomyelin polarized at the front, forming cholesterol (chol)- and sphingomyelin/cholesterol (SM/chol)-enriched domains, while GM1-enriched domains polarized at the rear. A comparison of domain proportion suggested that SM/chol- and GM1-enriched domains originated from the SM/chol/GM1-coenriched domains found at resting state. Modulation of domain proportion (through cholesterol depletion, combined or not with actin polymerization inhibition, or sphingolipid synthesis inhibition) revealed that the higher the chol- and SM/chol-enriched domains, the higher the myoblast migration. At the front, chol- and SM/chol-enriched domains were found in proximity with F-actin fibers and the lateral mobility of sphingomyelin in domains was specifically restricted in a cholesterol- and cytoskeleton-dependent manner while domain abrogation impaired F-actin and focal adhesion polarization. Altogether, we showed the polarization of cholesterol and sphingomyelin and their clustering in chol- and SM/chol-enriched domains with differential properties and roles, providing a mechanism for the spatial and functional control of myoblast migration.https://www.mdpi.com/2218-273X/13/2/319membrane lateral heterogeneityAiryscan microscopyatomic force microscopyGM1 gangliosidefocal adhesionactin cytoskeleton |
| spellingShingle | Juliette Vanderroost Noémie Avalosse Danahe Mohammed Delia Hoffmann Patrick Henriet Christophe E. Pierreux David Alsteens Donatienne Tyteca Cholesterol and Sphingomyelin Polarize at the Leading Edge of Migrating Myoblasts and Involve Their Clustering in Submicrometric Domains Biomolecules membrane lateral heterogeneity Airyscan microscopy atomic force microscopy GM1 ganglioside focal adhesion actin cytoskeleton |
| title | Cholesterol and Sphingomyelin Polarize at the Leading Edge of Migrating Myoblasts and Involve Their Clustering in Submicrometric Domains |
| title_full | Cholesterol and Sphingomyelin Polarize at the Leading Edge of Migrating Myoblasts and Involve Their Clustering in Submicrometric Domains |
| title_fullStr | Cholesterol and Sphingomyelin Polarize at the Leading Edge of Migrating Myoblasts and Involve Their Clustering in Submicrometric Domains |
| title_full_unstemmed | Cholesterol and Sphingomyelin Polarize at the Leading Edge of Migrating Myoblasts and Involve Their Clustering in Submicrometric Domains |
| title_short | Cholesterol and Sphingomyelin Polarize at the Leading Edge of Migrating Myoblasts and Involve Their Clustering in Submicrometric Domains |
| title_sort | cholesterol and sphingomyelin polarize at the leading edge of migrating myoblasts and involve their clustering in submicrometric domains |
| topic | membrane lateral heterogeneity Airyscan microscopy atomic force microscopy GM1 ganglioside focal adhesion actin cytoskeleton |
| url | https://www.mdpi.com/2218-273X/13/2/319 |
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