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 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.
Mañes
S
S
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Campus de Cantoblanco, E-28049 Madrid, Spain. smanes@cnb.uam.es
Mira
E
E
Gómez-Moutón
C
C
Lacalle
R A
RA
Keller
P
P
Labrador
J P
JP
Martínez-A
C
C
D000230:Adenocarcinoma; D001943:Breast Neoplasms; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D002784:Cholesterol / Q000494:pharmacology / Q000502:physiology; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008563:Membrane Lipids / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000502:physiology; D019713:Receptors, CCR5 / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D008563:Membrane Lipids; D019713:Receptors, CCR5; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol; D017526:Receptor, IGF Type 1