Natural isolates of C. elegans show significant variation in their response to dauer pheromone. CB4507, a strain from the Anza Borrega Desert in California, is virtually nonresponsive to pheromone at temperatures below 25deg. However, like N2, it forms dauers without pheromone at 27deg. Thus, the dauer defect in this strain appears to be specific to pheromone response and not temperature response. We found that the pheromone-insensitive phenotype of CB4507 could be mapped to a single locus (
sa935 ) on chromosome V. Additionally,
sa935 partially suppresses the Daf-c phenotype of
daf-7 and
daf-14 (in the TGF- b branch of the dauer pathway) but not
daf-11 or
daf-2 (in other branches). Mutations in the gene
scd-2 also map to chromosome V, suppress TGF- b branch mutations and are pheromone-insensitive. Complementation tests showed that
sa935 is an allele of
scd-2 . We cloned
scd-2 and found that it encodes a receptor tyrosine kinase most closely related to the human oncogenes ALK and LTK.
sa935 leads to substitution of arginine for glycine near the N-terminus of the kinase domain. This glycine is strongly conserved in protein kinases and is essential for kinase activity. Thus,
sa935 is predicted to result in a kinase-null form of the SCD-2 protein. The two EMS-induced
scd-2 alleles have mutations in the kinase domain and a splice-site. Thus, none of the alleles are predicted to be null. Consistent with the possibility that SCD-2 has a kinase-independent function, there are isoforms of human LTK lacking the kinase domain. Like
scd-2 , mutations in
scd-1 suppress the Daf-c phenotype of TGF- b branch mutants. However,
scd-1 mutations do not affect pheromone response, but are stronger suppressors of the TGF- b branch mutants and suppress other pleiotropies of these mutants as well. We cloned
scd-1 and found that it encodes a novel protein with several regions that are extremely glutamine (Q) rich. Within these regions, there are long runs of Q interspersed with other amino acids, usually alanine. The longest pure poly-Q run is 8 amino acids. The C. briggsae
scd-1 homolog has many differences from C. elegans within the Q-rich regions. A
scd-1::gfp fusion is expressed in many tissues, most notably hypodermis and neurons. Expression of constructs carrying the Q-rich regions is cytoplasmic, with a distinctly speckled and stringy appearance. This localization pattern appears to depend on the presence of the Q-rich regions and may be a result of protein aggregation.