title: Distinct regions within fibulin-1D modulate interactions with hemicentin.
abstract: Fibulins are evolutionarily conserved extracellular matrix (ECM) proteins that assemble in elastic fibers and basement membranes. Caenorhabditis elegans has a single fibulin gene that produces orthologs of vertebrate fibulin-1 C and D splice forms. In a structure-function analysis of fibulin-1 domains, a series of deletion constructs show that EGF repeats 4 and 5 are required for the hemicentin-dependent assembly and function of fibulin-1D in native locations. In contrast, constructs missing the second EGF repeat of fibulin-1D (EGF2D) assemble in ectopic locations in a hemicentin dependent manner. Constructs that contain EGF2D are cleaved into two fragments, but constructs with EGF2D missing are not, suggesting that a protease binds and/or cleaves fibulin-1D at a site that is likely within EGF2D. Together, the data suggests that EGF repeats 4 and 5 promote interaction with hemicentin while a region within EGF2D suppresses ectopic interactions with hemicentin and this suppression may be protease dependent.
authors.affiliation: Center for Biomedical Engineering and Technology and Department of Physiology, University of Maryland School of Medicine, University of Maryland, Baltimore 725 W. Lombard St., Baltimore, MD 21201, USA.
authors.forename: Joaquin M
authors.initials: JM
authors.lastname: Muriel
authors.forename: Chun
authors.initials: C
authors.lastname: Dong
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Vogel
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; C060820:fibulin; C424064:him-4 protein, C elegans