title: Complex patterns of alternative splicing mediate the spatial and temporal distribution of perlecan/UNC-52 in Caenorhabditis elegans.
abstract: The unc-52 gene encodes the nematode homologue of mammalian perlecan, the major heparan sulfate proteoglycan of the extracellular matrix. This is a large complex protein with regions similar to low-density lipoprotein receptors, laminin, and neural cell adhesion molecules (NCAMs). In this study, we extend our earlier work and demonstrate that a number of complex isoforms of this protein are expressed through alternative splicing. We identified three major classes of perlecan isoforms: a short form lacking the NCAM region and the C-terminal agrin-like region; a medium form containing the NCAM region, but still lacking the agrin-like region; and a newly identified long form that contains all five domains present in mammalian perlecan. Using region-specific antibodies and unc-52 mutants, we reveal a complex spatial and temporal expression pattern for these UNC-52 isoforms. As well, using a series of mutations affecting different regions and thus different isoforms of UNC-52, we demonstrate that the medium NCAM-containing isoforms are sufficient for myofilament lattice assembly in developing nematode body-wall muscle. Neither short isoforms nor isoforms containing the C-terminal agrin-like region are essential for sarcomere assembly or muscle cell attachment, and their role in development remains unclear.
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4.
authors.forename: G P
authors.initials: GP
authors.lastname: Mullen
authors.forename: T M
authors.initials: TM
authors.lastname: Rogalski
authors.forename: J A
authors.initials: JA
authors.lastname: Bush
authors.forename: P R
authors.initials: PR
authors.lastname: Gorji
authors.forename: D G
authors.initials: DG
authors.lastname: Moerman
mesh_terms: D018171:Agrin / Q000737:chemistry; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D012734:Disorders of Sex Development; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D024510:Muscle Development; D009154:Mutation; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry; D020033:Protein Isoforms; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017384:Sequence Deletion
chemical_list: D018171:Agrin; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D008565:Membrane Proteins; D019006:Neural Cell Adhesion Molecules; D020033:Protein Isoforms; D011509:Proteoglycans; C082396:unc-52 protein, C elegans; C071927:perlecan