Growth control by EGF repeats of the C. elegans Fibulin-1C isoform.
Fibulin is a broadly conserved component of the extracellular matrix (ECM). Previous studies have shown that Caenorhabditis elegans FIBULIN-1 (FBL-1) controls the width of the gonad (Hesselson, D., C. Newman, K.W. Kim, and J. Kimble. 2004. Curr. Biol. 14:2005-2010; Kubota, Y., R. Kuroki, and K. Nishiwaki. 2004. Curr. Biol. 14:2011-2018; Muriel, J.M., C. Dong, H. Hutter, and B.E. Vogel. 2005. Development. 132: 4223-4234). In this study, we report that FBL-1 also controls developmental growth and that one isoform of fibulin-1, called FBL-1C, controls both functions by distinct mechanisms. A large FBL-1C fragment, including both epidermal growth factor (EGF) and fibulin-type C domains, is responsible for constraining gonadal width, but a much smaller fragment containing only two complete EGF repeats (EGF1-2C+) is critical for developmental growth. We suggest that the larger fragment serves a scaffolding function to stabilize the basement membrane and that the smaller fragment provides a regulatory function at the cell surface or within the ECM to control growth.
Hesselson
Daniel
D
Department of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
Kimble
Judith
J
D000818:Animals; D030801:Animals, Genetically Modified; D001485:Basement Membrane / Q000378:metabolism; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000737:chemistry*; D005109:Extracellular Matrix / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000254:growth & development*; D020033:Protein Isoforms; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D020033:Protein Isoforms; C060820:fibulin; D004815:Epidermal Growth Factor