CRSBP-1/LYVE-1 ligands stimulate contraction of the CRSBP-1-associated ER network in lymphatic endothelial cells

CRSBP-l/LYVE-1 ligands (PDGF-BB, VEGF-A165 and hyaluronic acid) have been shown to induce opening of lymphatic intercellular junctions in vitro and in vivo by stimulating contraction of lymphatic endothelial cells (LECs). The mechanism by which CRSBP-1 ligands stimulate contraction of LECs is not understood. Here we demonstrate that CRSBP-1 is localized to the plasma membrane as well as intracellular fibrillar structures in LECs, including primary human dermal LECs and SVEC4-10 cells. CRSBP-1-associated fibrillar structures are identical to the ER network as evidenced by the co-localization of CRSBP-1 and BiP in these cells. CRSBP-1 ligands stimulate contraction of the ER network in a CRSBP-1-dependent and paclitaxel (a microtubule-stabilizing agent)-sensitive manner. These results suggest that ligand-stimulated ER contraction is associated with ligand-stimulated contraction in LECs.

► CRSBP-1 ligands induce opening of lymphatic intercellular junctions.
► We examine the mechanism by which CRSBP-1 ligands exert such activity.
► CRSBP-1 is localized to the plasma membrane and ER network in endothelial cells.
► CRSBP-1 ligands stimulate contraction of the ER network in a Taxol-sensitive manner.
► Ligand-induced ER contraction is associated with ligand-induced cell contraction.