MADD-2, a homolog of the Opitz syndrome protein MID1, regulates guidance to the midline through UNC-40 in Caenorhabditis elegans

Mariam Alexander; Guillermo Selman; Ashwin Seetharaman; Kevin Ka Ming Chan; Serena Ann D'Souza; Alexandra B Byrne; Peter J Roy

doi:10.1016/j.devcel.2010.05.016

MADD-2, a homolog of the Opitz syndrome protein MID1, regulates guidance to the midline through UNC-40 in Caenorhabditis elegans

Dev Cell. 2010 Jun 15;18(6):961-72. doi: 10.1016/j.devcel.2010.05.016.

Authors

Mariam Alexander¹, Guillermo Selman, Ashwin Seetharaman, Kevin Ka Ming Chan, Serena Ann D'Souza, Alexandra B Byrne, Peter J Roy

Affiliation

¹ Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.

PMID: 20627078
DOI: 10.1016/j.devcel.2010.05.016

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Body Patterning / physiology
Caenorhabditis elegans / cytology
Caenorhabditis elegans / embryology*
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / isolation & purification
Caenorhabditis elegans Proteins / metabolism*
Cell Adhesion Molecules / genetics
Cell Adhesion Molecules / metabolism*
Cell Differentiation / physiology
Functional Laterality / physiology
Gene Expression Regulation, Developmental / physiology
Growth Cones / metabolism
Growth Cones / ultrastructure
Humans
Microtubule Proteins / genetics
Microtubule Proteins / metabolism*
Motor Neurons / cytology
Motor Neurons / metabolism
Muscle, Striated / cytology
Muscle, Striated / embryology
Muscle, Striated / metabolism
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism
Nervous System / cytology
Nervous System / embryology*
Nervous System / metabolism
Neuromuscular Junction / cytology
Neuromuscular Junction / embryology
Neuromuscular Junction / metabolism
Nuclear Proteins / genetics
Nuclear Proteins / isolation & purification
Nuclear Proteins / metabolism*
Transcription Factors / genetics
Transcription Factors / metabolism*
Ubiquitin-Protein Ligases

Substances

Caenorhabditis elegans Proteins
Cell Adhesion Molecules
Microtubule Proteins
Nerve Tissue Proteins
Nuclear Proteins
Transcription Factors
UNC-40 protein, C elegans
UNC-73 protein, C elegans
MID1 protein, human
Ubiquitin-Protein Ligases