Worm Breeder's Gazette 12(2): 55 (January 1, 1992)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

The daf-4 Gene Encodes a Receptor Serine Kinase Similar to the Activin Receptor

Miguel Estevez, Patrice S. Albert, Donald L. Riddle

Molecular Biology Program, University of Missouri, Columbia, Missouri 65211

Mutants affected in the decision to form dauer larvae are either dauer-constitutive, which form dauer larvae in abundant food, or dauer-defective, which cannot form dauer larvae when starved. Interactions between specific dauer-constitutive and dauer-defective mutants have been used to construct a pathway for gene action. daf-4 ,a dauer-constitutive gene near the end of the pathway was cloned by transposon tagging. Sequences flanking the transposon insertion site were used to isolate genomic and cDNA clones. Microinjection of one of the genomic clones into the germline of daf-4 mutants transforms their progeny to wild-type, demonstrating that the cloned DNA conveys daf-4 function. The cDNA's encode a kinase 33% identical to the kinase domain of the daf-1 transmembrane receptor kinase (Georgi et al., Cell 61:635, 1990), and 40% identical to the kinase domain of the activin receptor (Matthews and Vale, Cell 65:973, 1991). A daf-4 hydrophobicity plot suggests it has transmembrane and extracellular domains. It is intriguing that the putative extracellular domains of the daf-4 and daf-1 proteins share a short cysteine-rich sequence motif with the activin receptor and the TGF-ß1 binding protein.

It is possible that the daf-1 and daf-4 proteins are C. elegans homologs of the mammalian type I and type II TGF-ß receptors previously proposed by Laiho et al. (JBC 265:18518,1990). Thus, the pathway of signal transduction that regulates development of the C. elegans dauer larva may be the nematode analogue of a TGF-ß signalling system. The daf-12 gene specifies what we believe to be the last step in signal transduction. It encodes a member of the steroid/thyroid hormone receptor superfamily. Its sequence appears to be most similar to the human Vitamin D and Retinoic Acid receptors (Yeh and Riddle, 1991 C. elegans Meeting abstracts, p. 349). Whereas daf-1 and daf-4 are required for normal non-dauer development, daf-12 activity is required for dauer larva morphogenesis. We propose that the activin-receptor-like daf kinases phosphorylate proteins that promote growth, and directly or indirectly inactivate the daf-12 receptor, possibly by preventing synthesis of a dauer-inducing hormone.