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.
Department of Zoology, University of British Columbia, Vancouver, Canada.
T M
TM
Rogalski
B D
BD
Williams
G P
GP
Mullen
D G
DG
Moerman
D008841:Actin Cytoskeleton / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001485:Basement Membrane / Q000737:chemistry*; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004251:DNA Transposable Elements; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000737:chemistry* / Q000235:genetics; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000737:chemistry* / Q000235:genetics; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics; D007797:Laminin / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000235:genetics; D009124:Muscle Proteins / Q000737:chemistry*; D016254:Mutagenesis, Insertional; D016366:Open Reading Frames; D011509:Proteoglycans / Q000737:chemistry* / Q000235:genetics; D011973:Receptors, LDL / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; D015816:Cell Adhesion Molecules, Neuronal; D004251:DNA Transposable Elements; D015801:Helminth Proteins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D007136:Immunoglobulins; D007797:Laminin; D008565:Membrane Proteins; D009124:Muscle Proteins; D011509:Proteoglycans; D011973:Receptors, LDL; D011993:Recombinant Fusion Proteins; C082396:unc-52 protein, C elegans; C071927:perlecan