A homologue of the Drosophila kinesin-like protein Costal2 regulates Hedgehog signal transduction in the vertebrate embryo.
Orthologues of nearly all of the core components of the Hedgehog signalling pathway, defined originally through genetic analysis in Drosophila, have now been discovered in vertebrates and shown to have highly conserved functions. The one striking exception to this rule is the kinesin-like protein Costal2, which plays a central role in controlling the activity of the zinc-finger-containing transcriptional regulator, Cubitus interruptus that modulates all Hedgehog-dependent target gene expression, but whose involvement in Hedgehog signalling has not been demonstrated in vertebrates. We report the cloning of a kinesin-related gene from the zebrafish that in structure as well as function, appears to represent the first vertebrate orthologue of costal2. Using a combination of genetic and biochemical analysis, we provide evidence that as in Drosophila, zebrafish Costal2 acts principally as an intracellular repressor of signal transduction, in conjunction with Suppressor of Fused, another protein that negatively regulates signalling in Hedgehog-responsive cells.
Tay
Shang Yew
SY
Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore 138673.
Ingham
Philip W
PW
Roy
Sudipto
S
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D053823:Hedgehog Proteins; D016547:Kinesins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism; D016335:Zinc Fingers / Q000502:physiology
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; C499749:Kif7 protein, zebrafish; D012097:Repressor Proteins; C097059:Su(fu) protein, Drosophila; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; C092937:ci protein, Drosophila; C107452:cos protein, Drosophila; C077245:hh protein, Drosophila; D016547:Kinesins