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: The mechanism by which the receptor UNC-40 (DCC) polarizes toward its ligand UNC-6 (netrin) to mediate diverse guidance functions is poorly understood. Using C. elegans AC invasion as a model for UNC-40/UNC-6 polarization, we have found that in the absence of UNC-6, UNC-40 is active, generates F-actin, and undergoes oscillatory clustering characterized by repeated cycles of cluster assembly and disassembly at different regions of the cell surface. We show that UNC-6 orients and stabilizes UNC-40 clustering, and that the protein MADD-2, a direct regulator of UNC-40, promotes UNC-40 clustering and the ability of UNC-40 to polarize toward UNC-6. Together, our data suggest that UNC-6 (netrin) directs polarized responses by stabilizing the localization of oscillatory clustering of the DCC receptor (Fig. 9).
Affiliation: Department of Biology, Duke University, Durham, NC 27708.