title: Developmental role of zebrafish protease-activated receptor 1 (PAR1) in the cardio-vascular system.
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 results demonstrate a high degree of conservation of PAR1 proteins in the vertebrate lineage in respect to amino acid sequence as well as protein function.
authors.affiliation: Biozentrum der Universität Basel, Growth and Development, Basel, Switzerland.
authors.forename: Elin
authors.initials: E
authors.lastname: Ellertsdottir
authors.forename: Peter R
authors.initials: PR
authors.lastname: Berthold
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bouzaffour
authors.forename: Pascale
authors.initials: P
authors.lastname: Dufourcq
authors.forename: Vincent
authors.initials: V
authors.lastname: Trayer
authors.forename: Carole
authors.initials: C
authors.lastname: Gauron
authors.forename: Sophie
authors.initials: S
authors.lastname: Vriz
authors.forename: Markus
authors.initials: M
authors.lastname: Affolter
authors.forename: Christine
authors.initials: C
authors.lastname: Rampon
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000196:embryology*; D019143:Evolution, Molecular; D055785:Gene Knockdown Techniques; D006339:Heart Rate; D044463:Receptor, PAR-1 / Q000235:genetics / Q000502:physiology*; D012039:Regional Blood Flow; D015027:Zebrafish / Q000196:embryology*
chemical_list: D044463:Receptor, PAR-1