title: Selective assembly of fibulin-1 splice variants reveals distinct extracellular matrix networks and novel functions for perlecan/UNC-52 splice variants.
abstract: Fibulin-1C and fibulin-1D splice variants have been conserved throughout metazoan evolution and have distinct functions in Caenorhabditis elegans development. Both splice variants are required for the assembly of hemidesmosome-mediated mechanosensory neuron and uterine attachments, although the molecular associations that underlie their distinct functions at these locations are not known. Here, we show that the assembly of fibulin-1C and fibulin-1D splice variants at these anchorages is dependent upon distinct components of the extracellular matrix (ECM): Fibulin-1D assembly at uterine and mechanosensory neurons attachments is dependent upon a perlecan/ UNC-52 splice variant that includes alternately spliced IG8-IG10, whereas the assembly of fibulin-1C at mechanosensory neuron attachments is dependent upon laminin/ EPI-1. These data not only indicate that fibulin-1C and fibulin-1D are components of distinct networks of ECM but also demonstrates a novel function for a major class of perlecan splice variants found in C. elegans and mouse. In addition, we demonstrate that overexpression of another ECM protein, collagen XVIII, can suppress gonad morphogenesis defects associated with loss of fibulin-1C, suggesting that some genetic defects that result in a weakened basement membrane can be compensated by overexpression of genes for ECM components that stabilize basement membranes.
authors.affiliation: Program in Cell Structure and Development, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland, USA.
authors.forename: Joaquin M
authors.initials: JM
authors.lastname: Muriel
authors.forename: Xuehong
authors.initials: X
authors.lastname: Xu
authors.forename: James M
authors.initials: JM
authors.lastname: Kramer
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Vogel
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D043170:Collagen Type XVIII / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism* / Q000502:physiology; D006066:Gonads / Q000378:metabolism / Q000473:pathology; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics* / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008857:Microscopy, Interference / Q000379:methods; D008954:Models, Biological; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D043170:Collagen Type XVIII; D019812:Heparan Sulfate Proteoglycans; D007797:Laminin; D008565:Membrane Proteins; D020033:Protein Isoforms; D011509:Proteoglycans; C060820:fibulin; C082396:unc-52 protein, C elegans; C071927:perlecan