C. elegans seu-1 encodes novel nuclear proteins that regulate responses to UNC-6/netrin guidance cues.
In C. elegans, ectopic expression of the UNC-5 netrin receptor is sufficient to cause repulsion of growth cones and cells away from ventral sources of the UNC-6/netrin guidance cue. A genetic suppressor screen identified the seu-1 gene as required for repulsion of touch neuron growth cones ectopically expressing unc-5. We report here that seu-1 mutations also enhance the frequency of distal tip cell migrations of unc-5 or unc-40 mutants. The seu-1 gene encodes two novel proteins (SEU-1A and SEU-1B) containing a charged central domain and several regions of low amino acid complexity. Transgenic rescue experiments indicate that seu-1 can act cell autonomously in the touch neurons and distal tip cells and that SEU-1 function requires both the SEU-1A and SEU-1B isoforms. A GFP fusion construct was expressed in a dynamic pattern throughout development and localized in the nuclei of neuronal and non-neuronal cells, including gonadal leader cells. These results implicate nuclear SEU-1 in the interpretation of UNC-6/netrin directional information by migrating growth cones and cells.
Zheng
Hong
H
Department of Medical and Molecular Genetics, Faculty of Medicine, University of Toronto, and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Coudiere
Ludivine
L
Camia
Cheryl
C
Colavita
Antonio
A
Culotti
Joseph G
JG
Merz
David C
DC
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000075386:Netrin Receptors; D000075385:Netrins; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D000075385:Netrins; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; C525056:Seu-1 protein, C elegans; C078146:UNC-6 protein, C elegans