Fiche publication
Date publication
mars 2020
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MELY Yves
Tous les auteurs :
Kishimoto T, Tomishige N, Murate M, Ishitsuka R, Schaller H, Mély Y, Ueda K, Kobayashi T
Lien Pubmed
Résumé
During adhesion, cells develop filopodia to facilitate the attachment to the extracellular matrix. The small guanosine triphosphate (GTP)-binding protein, Cdc42, plays a central role in the formation of filopodia. It has been reported that Cdc42 activity is regulated by cholesterol (Chol). We examined Chol distribution in filopodia using Chol-binding domain 4 (D4) fragment of bacterial toxin, perfringolysin O that senses high membrane concentration of Chol. Our results indicate that fluorescent D4 was enriched at the tip of the outer leaflet of filopodia in the initiation phase of cell adhesion. This enrichment was accompanied by a defect of D4 labeling in the inner leaflet. Steady phase adhered cell experiment indicated that both Cdc42 and ATP-binding cassette transporter, ABCA1, were involved in the binding of D4 to the cell surface. Depletion of Chol activated Cdc42. Our results suggest that asymmetric distribution of Chol at the tip of filopodia induces activation of Cdc42, and thus, facilitates filopodia formation.
Mots clés
ABCA1, Cdc42, cholesterol probe, lipid asymmetry
Référence
FASEB J.. 2020 Mar 12;:
