title: Engulfed cadherin fingers are polarized junctional structures between collectively migrating endothelial cells.
abstract: The development and maintenance of tissues requires collective cell movement, during which neighbouring cells coordinate the polarity of their migration machineries. Here, we ask how polarity signals are transmitted from one cell to another across symmetrical cadherin junctions, during collective migration. We demonstrate that collectively migrating endothelial cells have polarized VE-cadherin-rich membrane protrusions, 'cadherin fingers', which leading cells extend from their rear and follower cells engulf at their front, thereby generating opposite membrane curvatures and asymmetric recruitment of curvature-sensing proteins. In follower cells, engulfment of cadherin fingers occurs along with the formation of a lamellipodia-like zone with low actomyosin contractility, and requires VE-cadherin/catenin complexes and Arp2/3-driven actin polymerization. Lateral accumulation of cadherin fingers in follower cells precedes turning, and increased actomyosin contractility can initiate cadherin finger extension as well as engulfment by a neighbouring cell, to promote follower behaviour. We propose that cadherin fingers serve as guidance cues that direct collective cell migration.
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Arnold
authors.identifier: http://orcid.org/0000-0001-7808-8880
authors.initials: A
authors.lastname: Hayer
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Shao
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Mingyu
authors.identifier: http://orcid.org/0000-0003-1718-6203
authors.initials: M
authors.lastname: Chung
authors.affiliation: Cell Sciences Imaging Facility, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Lydia-Marie
authors.initials: LM
authors.lastname: Joubert
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Hee Won
authors.identifier: http://orcid.org/0000-0002-0000-8091
authors.initials: HW
authors.lastname: Yang
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Feng-Chiao
authors.initials: FC
authors.lastname: Tsai
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Anjali
authors.identifier: http://orcid.org/0000-0002-9709-9558
authors.initials: A
authors.lastname: Bisaria
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Betzig
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Meyer
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins / Q000378:metabolism; D002452:Cell Count; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D016764:Cell Polarity; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D007365:Intercellular Junctions / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D062308:Optogenetics; D010587:Phagocytosis; D058105:Polymerization; D011554:Pseudopodia / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000205:Actomyosin; D015703:Antigens, CD; D015820:Cadherins; D051177:Catenins; D000099152:Cadherin 5