RGS proteins inhibit Xwnt-8 signaling in Xenopus embryonic development.
RGS family members are GTPase activating proteins (GAPs) that antagonize signaling by heterotrimeric G proteins. Injection of Xenopus embryos with RNA encoding rat RGS4 (rRGS4), a GAP for G(i) and G(q), resulted in shortened trunks and decreased skeletal muscle. This phenotype is nearly identical to the effect of injection of either frzb or dominant negative Xwnt-8. Injection of human RGS2, which selectively deactivates G(q), had similar effects. rRGS4 inhibited the ability of early Xwnt-8 but not Xdsh misexpression to cause axis duplication. This effect is distinct from axin family members that contain RGS-like domains but act downstream of Xdsh. We identified two Xenopus RGS4 homologs, one of which, Xrgs4a, was expressed as a Spemann organizer component. Injection of Xenopus embryos with Xrgs4a also resulted in shortened trunks and decreased skeletal muscle. These results suggest that RGS proteins modulate Xwnt-8 signaling by attenuating the function of a G protein.
Wu
C
C
Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Zeng
Q
Q
Blumer
K J
KJ
Muslin
A J
AJ
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D005799:Genes, Dominant; D006023:Glycoproteins; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008845:Microinjections; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D010957:Plasmids; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D020710:RGS Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D051153:Wnt Proteins; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D000099274:Frizzled-Related Proteins
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D019204:GTP-Binding Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020710:RGS Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D000099274:Frizzled-Related Proteins; C000606586:DVL1 protein, Xenopus; C105345:Rgs2 protein, mouse; C495248:wnt8a protein, Xenopus; C098799:RGS4 protein