THE MEC-8 GENE OF CAENORHABDITIS-ELEGANS AFFECTS MUSCLE AND SENSORY NEURON FUNCTION AND INTERACTS WITH 3 OTHER GENES - UNC-52, SMU-1 AND SMU-2

Mutations in the Caenorhabditis elegans gene mec-8 were previously sho wn to cause defects in mechanosensation and in the structure and dye f illing of certain chemosensory neurons. Using noncomplementation scree ns, we have identified eight new mec-8 alleles and a deficiency that u ncovers the locus. Strong mec-8 mutants exhibit an incompletely penetr ant cold-sensitive embryonic and larval arrest, which we have correlat ed with defects in the attachment of body muscle to the hypodermis and cuticle. Mutations in mec-8 strongly enhance the mutant phenotype of unc-52(viable) mutations; double mutants exhibit an unconditional arre st and paralysis at the twofold stage of embryonic elongation, a pheno type characteristic of lethal alleles of unc-52, a gene previously sho wn to encode a homolog of the core protein of heparan sulfate proteogy lcan, found in basement membrane, and to be involved in the anchorage of myofilament lattice to the muscle cell membrane. We have identified and characterized four extragenic recessive suppressors of a mec-8; u nc-52(viable) synthetic lethality. The suppressors, which define the g enes smu-1 and smu-2, can weakly suppress all mec-8 mutant phenes. The y also suppress the muscular dystrophy conferred by an unc-52(viable) mutation.