DAF-5 is a Ski oncoprotein homolog that functions in a neuronal TGF beta pathway to regulate C. elegans dauer development.
An unconventional TGF beta superfamily pathway plays a crucial role in the decision between dauer diapause and reproductive growth. We have studied the daf-5 gene, which, along with the daf-3 Smad gene, is antagonized by upstream receptors and receptor-regulated Smads. We show that DAF-5 is a novel member of the Sno/Ski superfamily that binds to DAF-3 Smad, suggesting that DAF-5, like Sno/Ski, is a regulator of transcription in a TGF beta superfamily signaling pathway. However, we present evidence that DAF-5 is an unconventional Sno/Ski protein, because DAF-5 acts as a co-factor, rather than an antagonist, of a Smad protein. We show that expressing DAF-5 in the nervous system rescues a daf-5 mutant, whereas muscle or hypodermal expression does not. Previous work suggested that DAF-5 and DAF-3 function in pharyngeal muscle to regulate gene expression, but our analysis of regulation of a pharynx specific promoter suggests otherwise. We present a model in which DAF-5 and DAF-3 control the production or release of a hormone from the nervous system by either regulating the expression of biosynthetic genes or by altering the connectivity or the differentiated state of neurons.
da Graca
Li S
LS
Department of Biochemistry and Molecular Biology, Rutgers University, Piscataway, NJ 08854, USA.
Zimmerman
Karen K
KK
Mitchell
Melissa C
MC
Kozhan-Gorodetska
Marianne
M
Sekiewicz
Kamila
K
Morales
Yairani
Y
Patterson
Garth I
GI
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D010058:Oviposition; D010614:Pharynx / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D016212:Transforming Growth Factor beta; C446031:rasp protein, Drosophila; D000217:Acyltransferases