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Development. 2014 Nov;141(22):4395-405. doi: 10.1242/dev.110437.

The UNC-6/Netrin receptors UNC-40/DCC and UNC-5 inhibit growth cone filopodial protrusion via UNC-73/Trio, Rac-like GTPases and UNC-33/CRMP.

Author information

1
Programs in Genetics and Molecular, Cellular, and Developmental Biology, Department of Molecular Biosciences, The University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, USA.
2
Programs in Genetics and Molecular, Cellular, and Developmental Biology, Department of Molecular Biosciences, The University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, USA erikl@ku.edu.

Abstract

UNC-6/Netrin is a conserved axon guidance cue that can mediate both attraction and repulsion. We previously discovered that attractive UNC-40/DCC receptor signaling stimulates growth cone filopodial protrusion and that repulsive UNC-40-UNC-5 heterodimers inhibit filopodial protrusion in C. elegans. Here, we identify cytoplasmic signaling molecules required for UNC-6-mediated inhibition of filopodial protrusion involved in axon repulsion. We show that the Rac-like GTPases CED-10 and MIG-2, the Rac GTP exchange factor UNC-73/Trio, UNC-44/Ankyrin and UNC-33/CRMP act in inhibitory UNC-6 signaling. These molecules were required for the normal limitation of filopodial protrusion in developing growth cones and for inhibition of growth cone filopodial protrusion caused by activated MYR::UNC-40 and MYR::UNC-5 receptor signaling. Epistasis studies using activated CED-10 and MIG-2 indicated that UNC-44 and UNC-33 act downstream of the Rac-like GTPases in filopodial inhibition. UNC-73, UNC-33 and UNC-44 did not affect the accumulation of full-length UNC-5::GFP and UNC-40::GFP in growth cones, consistent with a model in which UNC-73, UNC-33 and UNC-44 influence cytoskeletal function during growth cone filopodial inhibition.

KEYWORDS:

Axon repulsion; Caenorhabditis elegans; Filopodia; Growth cone; UNC-40/DCC; UNC-5; UNC-6

PMID:
25371370
PMCID:
PMC4302909
DOI:
10.1242/dev.110437
[Indexed for MEDLINE]
Free PMC Article

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