UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity.
Bottom Line: By performing live-cell imaging of the DCC orthologue UNC-40 during anchor cell invasion in Caenorhabditis elegans, we have found that UNC-40 clusters, recruits F-actin effectors, and generates F-actin in the absence of UNC-6 (netrin).Together, our data suggest that UNC-6 (netrin) directs polarized responses by stabilizing UNC-40 clustering.We propose that ligand-independent UNC-40 clustering provides a robust and adaptable mechanism to polarize toward netrin.
Affiliation: Department of Biology, Duke University, Durham, NC 27708.Show MeSH
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Mentions: Considering the UNC-6–independent activity of UNC-40, we hypothesized that the ectopic F-actin found in unc-6 mutants might be directly organized by mislocalized, but active UNC-40. Supporting this idea, we found that F-actin patches were strongly colocalized with UNC-40 in both wild-type animals and unc-6 mutants (Fig. 2, A and B; and Fig. 3 D). In addition, a form of UNC-40 lacking the fourth and fifth FNIII repeats, which are necessary for UNC-6 binding (Geisbrecht et al., 2003; Kruger et al., 2004), was also active and mislocalized when expressed in both wild-type and unc-40 mutant ACs (Fig. 2, C–E; and Fig. 3 D). We also found that in the absence of UNC-6, F-actin patches colocalized tightly with membrane-localized clusters of UNC-40 downstream effectors (UNC-34, CED-10, MIG-2, and UNC-115; Fig. 3, A–D; Wang et al., 2014). This genetic, molecular, and colocalization analysis offers strong evidence that the UNC-40 receptor promotes F-actin formation in an UNC-6–independent manner.
Affiliation: Department of Biology, Duke University, Durham, NC 27708.