Membrane raft microdomains mediate front-rear polarity in migrating cells

The acquisition of spatial and functional asymmetry between the rear and the front of the cell is a necessary step for cell chemotaxis. Insulin‐like growth factor‐I (IGF‐I) stimulation of the human adenocarcinoma MCF‐7 induces a polarized phenotype characterized by asymmetrical CCR5 chemokine recept...

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Bibliographic Details
Published in:The EMBO journal 1999-11, Vol.18 (22), p.6211-6220
Main Authors: Mañes, Santos, Mira, Emilia, Gómez-Moutón, Concepción, Ana Lacalle, Rosa, Keller, Patrick, Pablo Labrador, Juan, Martínez-A, Carlos
Format: Article
Language:English
Subjects:
Adenocarcinoma
Breast Neoplasms
Cell Membrane - drug effects
Cell Membrane - physiology
Cell Membrane - ultrastructure
Cell Polarity - drug effects
Cell Polarity - physiology
chemokine receptor
chemotaxis
Chemotaxis - drug effects
Chemotaxis - physiology
Cholesterol - pharmacology
Cholesterol - physiology
Female
Humans
Insulin-Like Growth Factor I - pharmacology
leading edge
lipid rafts
Membrane Lipids - physiology
polarization
Receptor, IGF Type 1 - physiology
Receptors, CCR5 - physiology
Signal Transduction
Tumor Cells, Cultured
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Summary:The acquisition of spatial and functional asymmetry between the rear and the front of the cell is a necessary step for cell chemotaxis. Insulin‐like growth factor‐I (IGF‐I) stimulation of the human adenocarcinoma MCF‐7 induces a polarized phenotype characterized by asymmetrical CCR5 chemokine receptor redistribution to the leading cell edge. CCR5 associates with membrane raft microdomains, and its polarization parallels redistribution of raft molecules, including the raft‐associated ganglioside GM1, glycosylphosphatidylinositol‐anchored green fluorescent protein and ephrinB1, to the leading edge. The non‐raft proteins transferrin receptor and a mutant ephrinB1 are distributed homogeneously in migrating MCF‐7 cells, supporting the raft localization requirement for polarization. IGF‐I stimulation of cholesterol‐depleted cells induces projection of multiple pseudopodia over the entire cell periphery, indicating that raft disruption specifically affects the acquisition of cell polarity, but not IGF‐I‐induced protrusion activity. Cholesterol depletion inhibits MCF‐7 chemotaxis, which is restored by replenishing cholesterol. Our results indicate that initial segregation between raft and non‐raft membrane proteins mediates the necessary redistribution of specialized molecules for cell migration.
ISSN:0261-4189
1460-2075
DOI:10.1093/emboj/18.22.6211