developmental role of zebrafish protease-activated receptor 1 (par1) in the cardio-vascular system斑马鱼发育作用protease-activated受体1(par1)心血管系统.pdfVIP

Developmental Role of Zebrafish Protease-Activated Receptor 1 (PAR1) in the Cardio-Vascular System 1. 2. 2 2 2 Elin Ellertsdottir , Peter R. Berthold , Mohamed Bouzaffour , Pascale Dufourcq , Vincent Trayer , Carole Gauron3,4, Sophie Vriz2,3,4, Markus Affolter1, Christine Rampon2,3,4* ¨ ´ 1 Biozentrum der Universitat Basel, Growth and Development, Basel, Switzerland, 2 Univ Paris Diderot, Sorbonne Paris Cite, Paris, France, 3 Center for Interdisciplinary ´ Research in Biology, College de France, Paris, France, 4 Centre national de la recherche scientifique UMR 7241 and Institut National de la Sante et de la Recherche ´ Medicale, Paris, France Abstract Thrombin receptor, F2R or PAR1 is a G-protein coupled receptor, located in the membrane of endothelial cells. It has been initially found to transduce signals in hemostasis, but recently also known to act in cancer and in vascular development. Mouse embryos lacking PAR1 function die from hemorrhages with varying frequency at midgestation. We have performed a survey of potential PAR1 homologs in the zebrafish genome and identified a teleost ortholog of mammalian PAR1. Knockdown of par1 function in zebrafish embryos demonstrates a requirement for Par1 in cardio-vascular development. Furthermore, we show that function of Par1 requires the presence of a phylogenetically conserved proteolytic cleavage site and a second intracellular domain. Altogether our resul