title: GASP/WFIKKN proteins: evolutionary aspects of their functions.
abstract: Growth and differentiation factor Associated Serum Protein (GASP) 1 and 2 are proteins known to be involved in the control of myostatin activity at least in vitro. Most deuterostome GASPs share a modular organization including WAP, follistatin/kazal, IGc2, two kunitz, and NTR domains. Based on an exon shuffling model, we performed independent phylogenetic analyses on these modules and assessed that papilin is probably a sister sequence to GASP with a divergence date estimated from the last common ancestor to bilateria. The final organization was acquired by the addition of the FS domain in early deuterostomes. Our study revealed that Gasp genes diverged during the first round of genome duplication in early vertebrates. By evaluating the substitution rate at different sites on the proteins, we showed a better conservation of the follistatin/kazal domain of GASP1 than GASP2 in mammals, suggesting a stronger interaction with myostatin. We also observed a progressive increase in the conservation of follistatin and kunitz domains from the ancestor of Ciona to early vertebrates. In situ hybridization performed on mouse embryos showed a weak Gasp1 expression in the formed somites at 10.5 dpc and in limb buds from embryonic E10.0 to E12.5. Similar results were obtained for zebrafish embryos. We propose a synthetic view showing possible interactions between GASP1 and myostatin and highlighting the role of the second kunitz domain in preventing myostatin proteolysis.
authors.affiliation: INRA, UMR1061 Unité de Génétique Moléculaire Animale, Limoges, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Monestier
authors.forename: Caroline
authors.initials: C
authors.lastname: Brun
authors.forename: Olivier
authors.initials: O
authors.lastname: Cocquempot
authors.forename: Daniel
authors.initials: D
authors.lastname: Petit
authors.forename: Véronique
authors.initials: V
authors.lastname: Blanquet
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016678:Genome; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D055435:Myostatin / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish
chemical_list: D002352:Carrier Proteins; C479636:Gprasp1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D055435:Myostatin