title: EVA-1 functions as an UNC-40 Co-receptor to enhance attraction to the MADD-4 guidance cue in Caenorhabditis elegans.
abstract: We recently discovered a secreted and diffusible midline cue called MADD-4 (an ADAMTSL) that guides migrations along the dorsoventral axis of the nematode Caenorhabditis elegans. We showed that the transmembrane receptor, UNC-40 (DCC), whose canonical ligand is the UNC-6 (netrin) guidance cue, is required for extension towards MADD-4. Here, we demonstrate that MADD-4 interacts with an EVA-1/UNC-40 co-receptor complex to attract cell extensions. EVA-1 is a conserved transmembrane protein with predicted galactose-binding lectin domains. EVA-1 functions in the same pathway as MADD-4, physically interacts with both MADD-4 and UNC-40, and enhances UNC-40's sensitivity to the MADD-4 cue. This enhancement is especially important in the presence of UNC-6. In EVA-1's absence, UNC-6 interferes with UNC-40's responsiveness to MADD-4; in UNC-6's absence, UNC-40's responsiveness to MADD-4 is less dependent on EVA-1. By enabling UNC-40 to respond to MADD-4 in the presence of UNC-6, EVA-1 may increase the precision by which UNC-40-directed processes can reach their MADD-4-expressing targets within a field of the UNC-6 guidance cue.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kevin Ka Ming
authors.initials: KK
authors.lastname: Chan
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada; The Collaborative Programme in Developmental Biology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Seetharaman
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rachel
authors.initials: R
authors.lastname: Bagg
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Selman
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Joowan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada; The Collaborative Programme in Developmental Biology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Roy
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics; D002630:Chemotactic Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D009046:Motor Neurons; D024510:Muscle Development / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; C523438:EVA-1 protein, C elegans; C568399:MADD-4 protein, C elegans; D009419:Nerve Tissue Proteins; C102174:UNC-40 protein, C elegans