Products of the unc-52 gene in Caenorhabditis elegans are homologous to the core protein of the mammalian basement membrane heparan sulfate proteoglycan.

Mutations in the unc-52 gene of Caenorhabditis elegans affect attachment of the myofilament lattice to the muscle cell membrane. Here, we demonstrate that the unc-52 gene encodes a nematode homolog of perlecan, the mammalian basement membrane heparan sulfate proteoglycan. The longest potential open reading frame of this gene encodes a 2482-amino-acid 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 (domain III) 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 domain IV, whereas the smaller transcript encodes a shortened polypeptide that completely lacks domain IV. We have determined that the disorganized muscle phenotype observed in unc-52(st196) animals is caused by the insertion of a Tc1 transposon into domain IV. Two monoclonal antibodies that recognize an extracellular component of all contractile tissues in C. elegans fail to stain embryos homozygous for a lethal unc-52 allele. We have mapped the epitopes recognized by both monoclonal antibodies to a region of domain IV in the unc-52-encoded protein sequence.