%0 Journal Article %T Inter-Cellular Exchange of Cellular Components via VE-Cadherin-Dependent Trans-Endocytosis %A Takashi Sakurai %A Melissa J. Woolls %A Suk-Won Jin %A Masahiro Murakami %A Michael Simons %J PLOS ONE %D 2014 %I Public Library of Science (PLoS) %R 10.1371/journal.pone.0090736 %X 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. %U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0090736