deg-1 is a member of family of genes in which dominant mutations confer a phenotype of degeneration of specific neurons (Nature 349:588) . It encodes a putative membrane protein (Nature 345:410) that may act as a cell surface receptor for an as yet unknown ligand. We have observed interactions between different
deg-1 alleles in trans that suggest
deg-1 molecules can influence each other's functioning. The dominant, neurodegeneration-causing allele
u38 contains the same missense mutation (ala->val) as found in dominant, neurodegeneration- causing mutations of
mec-4. We have identified a second missense mutation,
u38u424, two codons downstream (gly- > arg) which inactivates the degeneration phenotype. Homozygous
u38u424 animals appear wild-type, however
u38u424/u38 + heterozygotes show partial, cold-sensitive suppression of the degeneration phenotype (WBG 11(4) :104). High copy number arrays of a
u38u424 genomic
deg-1 cosmid clone completely suppress two chromosomal copies of the
u38 allele, independent of temperature. These results suggest that the doubly mutant
deg-1 protein competes with the degeneration-causing isoform, either in the formation of
deg-1 protein multimers or in interactions with other molecules. The same
u38u424 high-copy arrays do not suppress
mec-4(
e161 1)-induced degenerations, suggesting that this competition does not involve the
mec-6 gene product.
mec-6 recessive mutations suppress both deg-l and
mec-4 dominant mutations (Nature 345:410). We have recently noticed a new behavioral phenotype associated with the
u38 mutation.
u38/+ heterozygotes continue to lay eggs after transfer to M9 buffer in microtitre wells.
u38 homozygotes are also egg-laying constitutive in this assay when compared to wild- type, but to a significantly lesser degree.
u38u424 and
deg-1 null alleles behave as wild-type in this assay. We are curious about the cellular focus of this phenotype, as well as the means by which it seems to be accentuated in trans by the wild-type allele. We will also report on progress in genomic sequencing that allows prediction of deg- 1 coding sequence upstream from that of the previously published partial cDNA clones (Nature 345:410), as well as sequence analysis of an EMS-induced deletion and of a Tc1 insertion mutation.