Cholesterol asymmetry at the tip of filopodia during cell adhesion.

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. © 2020 Federation of American Societies for Experimental Biology.

Citation

Takuma Kishimoto, Nario Tomishige, Motohide Murate, Reiko Ishitsuka, Hubert Schaller, Yves Mély, Kazumitsu Ueda, Toshihide Kobayashi. Cholesterol asymmetry at the tip of filopodia during cell adhesion. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2020 May;34(5):6185-6197

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PMID: 32162745

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