Semidominant mutations in
unc-105 cause hyper- contraction and paralysis of body-wall muscles. Molecular analysis of
unc-105 by B. Schrank in this laboratory showed that the
unc-105 gene product is a member of the degenerin family and shares homology with amiloride- sensitive sodium channels in mammalian tissues. Thus, UNC-105 protein may be part of a sodium channel that functions in muscle. Significantly, the hyper-contraction and paralysis phenotype of
unc-105 mutants can be completely suppressed by mutations in
sup-20. Early work by Park and Horvitz showed that these suppressor mutations are special alleles of the gene, and that null alleles of
sup-20 cause embryonic lethality (E. -C. Park and H. R. Horvitz, 1986). We have obtained several lines of evidence that suggest
sup-20 mutations are allelic to mutations in
let-2, a gene encoding the
a2 chain of the basement membrane-specific type IV collagen (M. H. Sibley, J. J. Johnson, C. C. Mello, and J. M. Kramer, 1993). First, both genes map to the same interval and mutations in
sup-20 and
let-2 show non-complementation. Second,
sup-20 mutations can be rescued by a cosmid carrying the wildtype
let-2 gene. Third, a mutational change in
let-2 sequence has been identified in
sup-20 mutants. These data suggest a functional link between a potential membrane sodium channel and the extracellualr matrix surrounding the membrane. It is plausible that the gating of this channel involves interaction with the basement membrane, and such interaction may serve as a 'stretch receptor' to transduce external mechanical signals to regulate muscle contraction.