title: Inter-cellular exchange of cellular components via VE-cadherin-dependent trans-endocytosis.
abstract: Cell-cell communications typically involve receptor-mediated signaling initiated by soluble or cell-bound ligands. Here, we report a unique mode of endocytosis: proteins originating from cell-cell junctions and cytosolic cellular components from the neighboring cell are internalized, leading to direct exchange of cellular components between two adjacent endothelial cells. VE-cadherins form transcellular bridges between two endothelial cells that are the basis of adherence junctions. At such adherens junction sites, we observed the movement of the entire VE-cadherin molecule from one endothelial cell into the other with junctional and cytoplasmic components. This phenomenon, here termed trans-endocytosis, requires the establishment of a VE-cadherin homodimer in trans with internalization proceeding in a Rac1-, and actomyosin-dependent manner. Importantly, the trans-endocytosis is not dependent on any known endocytic pathway including clathrin-dependent endocytosis, macropinocytosis or phagocytosis. This novel form of cell-cell communications, leading to a direct exchange of cellular components, was observed in 2D and 3D-cultured endothelial cells as well as in the developing zebrafish vasculature.
authors.affiliation: Yale Cardiovascular Research Center and Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Yale Cardiovascular Research Center and Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Woolls
authors.affiliation: Yale Cardiovascular Research Center and Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Suk-Won
authors.initials: SW
authors.lastname: Jin
authors.affiliation: Yale Cardiovascular Research Center and Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Yale Cardiovascular Research Center and Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America; Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Simons
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D019556:COS Cells; D015820:Cadherins / Q000378:metabolism*; D002450:Cell Communication; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D004705:Endocytosis; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D009218:Myosins / Q000378:metabolism; D021381:Protein Transport; D016596:Vinculin / Q000378:metabolism; D015027:Zebrafish; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D000199:Actins; D015703:Antigens, CD; D015820:Cadherins; D009218:Myosins; D016596:Vinculin; D020830:rac1 GTP-Binding Protein; D000099152:Cadherin 5