The minus‐end actin capping protein, UNC‐94/tropomodulin, regulates development of the Caenorhabditis elegans intestine

• Published in: Developmental dynamics 2014-06, Vol.243 (6), p.753-764
• Main Authors: Cox‐Paulson, Elisabeth, Cannataro, Vincent, Gallagher, Thomas, Hoffman, Corey, Mantione, Gary, Mcintosh, Matthew, Silva, Malan, Vissichelli, Nicole, Walker, Rachel, Simske, Jeffrey, Ono, Shoichiro, Hoops, Harold
• Format: Article
• Language: English
• Subjects: Actins - genetics; Actins - metabolism; actomyosin contractility; Animals; Caenorhabditis elegans - cytology; Caenorhabditis elegans - embryology; Caenorhabditis elegans - genetics; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - embryology; Intestines - cytology; Intestines - embryology; Mutation; Myosin Heavy Chains - genetics; Myosin Heavy Chains - metabolism; terminal web; Tropomodulin - genetics; Tropomodulin - metabolism; tubulogenesis
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.24118

Background: Tropomodulins are actin‐capping proteins that regulate the stability of the slow‐growing, minus‐ends of actin filaments. The C. elegans tropomodulin homolog, UNC‐94, has sequence and functional similarity to vertebrate tropomodulins. We investigated the role of UNC‐94 in C. elegans intestinal morphogenesis. Results: In the embryonic C. elegans intestine, UNC‐94 localizes to the terminal web, an actin‐ and intermediate filament‐rich structure that underlies the apical membrane. Loss of UNC‐94 function results in areas of flattened intestinal lumen. In worms homozygous for the strong loss‐of‐function allele, unc‐94(tm724), the terminal web is thinner and the amount of F‐actin is reduced, pointing to a role for UNC‐94 in regulating the structure of the terminal web. The non‐muscle myosin, NMY‐1, also localizes to the terminal web, and we present evidence that increasing actomyosin contractility by depleting the myosin phosphatase regulatory subunit, mel‐11, can rescue the flattened lumen phenotype of unc‐94 mutants. Conclusions: The data support a model in which minus‐end actin capping by UNC‐94 promotes proper F‐actin structure and contraction in the terminal web, yielding proper shape of the intestinal lumen. This establishes a new role for a tropomodulin in regulating lumen shape during tubulogenesis. Developmental Dynamics 243:753–764, 2014. © 2014 Wiley Periodicals, Inc. Key Findings UNC‐94 localizes to the intestinal terminal web in C. elegans embryos, where it modulates F‐actin levels. The C. elegans intestinal terminal web, like that of mammals, contains non‐muscle myosin. UNC‐94 supports actomyosin contractility in the intestinal terminal web, which is needed for proper lumen morphogenesis.