The Motor Protein Myosin-X Transports VE-Cadherin along Filopodia To Allow the Formation of Early Endothelial Cell-Cell Contacts MYOSIN-X TRANSPORT OF VE-CADHERIN ALONG FILOPODIA

• Published in: Molecular and cellular biology Vol. Apr. 2010
• Main Authors: Almagro, Sébastien, Durmort, Claire, Chervin-Pétinot, Adeline, Heyraud, Stéphanie, Dubois, Mathilde, Lambert, Olivier, Maillefaud, Camille, Hewat, Elizabeth, Schaal, Jean Patrick, Huber, Philippe, Gulino-Debrac, Danielle
• Format: Journal Article
• Language: English
• Published: American Society for Microbiology 01-02-2010
• Subjects: Cellular Biology; Life Sciences; actin cytoskeleton; VE-cadherin; videomicroscopy; transport; Myosin-X; filopodia
• ISSN: 0270-7306; 1098-5549
• DOI: 10.1128/MCB.01226-09

Vascular endothelium (VE), the monolayer of endothelial cells that lines the vascular tree, undergoes damage at the basis of some vascular diseases. Its integrity is maintained by VE-cadherin, an adhesive receptor localized at cell-cell junctions. Here, we show that VE-cadherin is also located at the tip and along filopodia in sparse or subconfluent endothelial cells. We observed that VE-cadherin navigates along intrafilopodial actin filaments. We found that the actin motor protein myosin-X is colocalized and moves synchronously with filopodial VE-cadherin. Immunoprecipitation and pulldown assays confirmed that myosin-X is directly associated with the VE-cadherin complex. Furthermore, expression of a dominant-negative mutant of myosin-X revealed that myosin-X is required for VE-cadherin export to cell edges and filopodia. These features indicate that myosin-X establishes a link between the actin cytoskeleton and VE-cadherin, thereby allowing VEcadherin transportation along intrafilopodial actin cables. In conclusion, we propose that VE-cadherin trafficking along filopodia using myosin-X motor protein is a prerequisite for cell-cell junction formation. This mechanism may have functional consequences for endothelium repair in pathological settings.