title: MADD-2, a homolog of the Opitz syndrome protein MID1, regulates guidance to the midline through UNC-40 in Caenorhabditis elegans.
abstract: The body muscles of Caenorhabditis elegans extend plasma membrane extensions called muscle arms to the midline motor axons to form the postsynaptic membrane of the neuromuscular junction. Through a screen for muscle arm development defective (Madd) mutants, we previously discovered that the UNC-40/DCC guidance receptor directs muscle arm extension through the Rho-GEF UNC-73. Here, we describe a gene identified through our mutant screen called madd-2, and show that it functions in an UNC-40 pathway. MADD-2 is a C1-TRIM protein and a homolog of human MID1, mutations in which cause Opitz Syndrome. We demonstrate that MADD-2 functions cell autonomously to direct muscle and axon extensions to the ventral midline of worms. Our results suggest that MADD-2 may enhance UNC-40 pathway activity by facilitating an interaction between UNC-40 and UNC-73. The analogous phenotypes that result from MADD-2 and MID1 mutations suggest that C1-TRIM proteins may have a conserved biological role in midline-oriented developmental events.
authors.affiliation: Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors.forename: Mariam
authors.initials: M
authors.lastname: Alexander
authors.forename: Guillermo
authors.initials: G
authors.lastname: Selman
authors.forename: Ashwin
authors.initials: A
authors.lastname: Seetharaman
authors.forename: Kevin Ka Ming
authors.initials: KK
authors.lastname: Chan
authors.forename: Serena Ann
authors.initials: SA
authors.lastname: D'Souza
authors.forename: Alexandra B
authors.initials: AB
authors.lastname: Byrne
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Roy
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008868:Microtubule Proteins / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D054792:Muscle, Striated / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009469:Neuromuscular Junction / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
chemical_list: D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D008868:Microtubule Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C102174:UNC-40 protein, C elegans; C111263:UNC-73 protein, C elegans; C109052:MID1 protein, human; D044767:Ubiquitin-Protein Ligases