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PLoS Genet. 2014 Aug 14;10(8):e1004521. doi: 10.1371/journal.pgen.1004521. eCollection 2014 Aug.

EVA-1 functions as an UNC-40 Co-receptor to enhance attraction to the MADD-4 guidance cue in Caenorhabditis elegans.

Author information

1
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
2
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.
3
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

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.

PMID:
25122090
PMCID:
PMC4133157
DOI:
10.1371/journal.pgen.1004521
[Indexed for MEDLINE]
Free PMC Article

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