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

• Authors: Elisabeth Cox-Paulson, State University of New York College Geneseo; Vincent Cannataro, State University of New York College Geneseo; Thomas Gallagher, State University of New York College Geneseo; Corey Hoffman, State University of New York College Geneseo; Gary Mantione, State University of New York College Geneseo; Matthew Mcintosh, State University of New York College Geneseo; Malan Silva, State University of New York College Geneseo; Nicole Vissichelli, State University of New York College Geneseo; Rachel Walker, State University of New York College Geneseo; Jeffrey Simske, Case Western Reserve University; Shoichiro Ono, Emory University; Harold Hoops, State University of New York College Geneseo
• Journal Title: Developmental Dynamics
• Volume: Volume 243, Number 6
• Publisher: Wiley: 12 months | 2014-06-01, Pages 753-764
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/dvdy.24118
• Subjects: Biology, Anatomy; Health Sciences, Pathology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Anatomy & Morphology; Developmental Biology; tubulogenesis; terminal web; actomyosin contractility; MEL-11 MYOSIN PHOSPHATASE; RHO-BINDING KINASE; BRUSH-BORDER; C-ELEGANS; INTERMEDIATE-FILAMENTS; TERMINAL WEB; EPITHELIAL MORPHOGENESIS; EMBRYONIC MORPHOGENESIS; TUBE MORPHOGENESIS; LUMEN INITIATION

Abstract

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.