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-A(165) 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.
Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Doisy Research Center, St. Louis, MO 63104, United States.
Wei-Hsien
WH
Hou
I-Hua
IH
Liua
Shuan Shian
SS
Huang
Jung San
JS
Huang
D000595:Amino Acid Sequence; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008024:Ligands; D042601:Lymphatic Vessels / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D017239:Paclitaxel / Q000494:pharmacology; D033921:Vesicular Transport Proteins / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; C119248:LYVE1 protein, human; D008024:Ligands; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; C091632:cell-surface retention-binding protein 1; D017239:Paclitaxel