In our analysis of mutations that block
mec-4(d)-induced degeneration of the six touch cells, we identified lesions in a gene that encodes a novel protein, with a low level of similarity to microtubule-associated proteins. This gene spans cosmids F08B6 and C37A2 and was originally predicted by the Genome Sequencing Consortium as being two separate genes (F08B6.5 and C37A2.5, on the two cosmids). Deletions of the gene cause animals to arrest growth early in development. We tested for complementation of lethal mutations in the region and determined that this gene corresponds to
let-398. It also appears to be allelic to
vms-1, an essential gene that genetically interacts with the kinesin-like gene
vab-8. Animals with lethal mutations in
vms-1 can be rescued by introduction of multiple copies of
vab-8 (vms:
vab-8 multicopy suppressible).
let-398/vms-1 is expressed broadly in the C. elegans nervous system including sensory neurons, interneurons and motor neurons of the ventral nerve cord. Additionally, strong expression is observed in the pharynx, the canal cell and some muscles. Interestingly, expression of the kinesin-like gene
vab-8 extensively overlaps with
let-398 expression. We have thus investigated the possibility that
vab-8 mutations might interfere with degenerative cell death. Examination of
mec-4(d);
vab-8 double mutants shows a marked decrease in degeneration of the six touch cells expressing the toxic
mec-4(d) allele. Our findings implicate a novel cytoskeletal component in biogenesis, function and/or stability of degenerin channels. Our working hypothesis is that
let-398 is involved in the intracellular trafficking of proteins across long neuron axons to their destined sub-cellular localization. We are currently in the process of evaluating this model by directly examining the sub-cellular localization and stability of MEC-4 and UNC-8 in the absence of LET-398/VMS-1 and VAB-8.