PRODUCTS OF THE UNC-52 GENE IN CAENORHABDITIS-ELEGANS ARE HOMOLOGOUS TO THE CORE PROTEIN OF THE MAMMALIAN BASEMENT-MEMBRANE HEPARAN-SULFATEPROTEOGLYCAN

Mutations in the unc-52 gene of Caenorhabditis elegans affect attachme nt of the myofilament lattice to the muscle cell membrane. Here, we de monstrate that the unc-52 gene encodes a nematode homolog of perlecan, the mammalian basement membrane heparan sulfate proteoglycan. The lon gest potential open reading frame of this gene encodes a 2482-amino-ac id protein with a signal peptide and four domains. The first domain is unique to the unc-52 polypeptide, whereas the three remaining domains contain sequences found in the LDL receptor (domain II) laminin (doma in II)) and N-CAM (domain IV). We have identified three alternatively spliced transcripts that encode different carboxy-terminal sequences. The two larger transcripts encode proteins containing all or part of d omain IV, whereas the smaller transcript encodes a shortened polypepti de that completely lacks domain IV. We have determined that the disorg anized muscle phenotype observed in unc-52(st196) animals is caused by the insertion of a Tc1 transposon into domain IV. Two monoclonal anti bodies that recognize an extracellular component of all contractile ti ssues in C. elegans fail to stain embryos homozygous for a lethal unc- 52 allele. We have mapped the epitopes recognized by both monoclonal a ntibodies to a region of domain IV in the unc-52-encoded protein seque nce.