Kermit, a frizzled interacting protein, regulates frizzled 3 signaling in neural crest development.
Wnts are a family of secreted glycoproteins that are important for multiple steps in early development. Accumulating evidence suggests that frizzled genes encode receptors for Wnts. However, the mechanism through which frizzleds transduce a signal and the immediate downstream components that convey that signal are unclear. We have identified a new protein, Kermit, that interacts specifically with the C-terminus of Xenopus frizzled-3 (Xfz3). Kermit is a 331 amino acid protein with a central PDZ domain. Kermit mRNA is expressed throughout Xenopus development and is localized to neural tissue in a pattern that overlaps Xfz3 expression temporally and spatially. Co-expression of Xfz3 and Kermit results in a dramatic translocation of Kermit to the plasma membrane. Inhibition of Kermit function with morpholino antisense oligonucleotides directed against the 5' untranslated region of Kermit mRNA blocks neural crest induction by Xfz3, and this is rescued by co-injection of mRNA encoding the Kermit open reading frame. These observations suggest that Kermit is required for Wnt/frizzled signaling in neural crest development. To the best of our knowledge, Kermit is the first protein identified that interacts directly with the cytoplasmic portion of frizzleds to modulate their signaling activity.
Tan
C
C
Department of Medicine (School of Medicine), University of Pennsylvania, Philadelphia, PA 19104, USA.
Deardorff
M A
MA
Saint-Jeannet
J P
JP
Yang
J
J
Arzoumanian
A
A
Klein
P S
PS
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian / Q000187:drug effects; D004627:Embryonic Induction / Q000235:genetics; D005260:Female; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009432:Neural Crest / Q000196:embryology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051153:Wnt Proteins; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C486340:FZD3 protein, Xenopus; C113865:FZD8 protein, Xenopus; D051157:Frizzled Receptors; C438192:GIPC1 protein, Xenopus; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins