title: The motor protein myosin-X transports VE-cadherin along filopodia to allow the formation of early endothelial cell-cell contacts.
abstract: 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 VE-cadherin 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.
authors.affiliation: iRTSV, APV, INSERM U882, CEA-Grenoble, 17 Rue des Martyrs, 38054 Grenoble Cedex 9, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Almagro
authors.forename: Claire
authors.initials: C
authors.lastname: Durmort
authors.forename: Adeline
authors.initials: A
authors.lastname: Chervin-Pétinot
authors.forename: Stephanie
authors.initials: S
authors.lastname: Heyraud
authors.forename: Mathilde
authors.initials: M
authors.lastname: Dubois
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambert
authors.forename: Camille
authors.initials: C
authors.lastname: Maillefaud
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hewat
authors.forename: Jean Patrick
authors.initials: JP
authors.lastname: Schaal
authors.forename: Philippe
authors.initials: P
authors.lastname: Huber
authors.forename: Danielle
authors.initials: D
authors.lastname: Gulino-Debrac
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D020285:Cryoelectron Microscopy; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000378:metabolism* / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D051177:Catenins; D009218:Myosins; D011993:Recombinant Fusion Proteins; D000099152:Cadherin 5; C498718:MYO10 protein, human