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Endocytosis of Wnt ligands from surrounding epithelial cells positions microtubule nucleation sites at dendrite branch points
Microtubule nucleation is important for microtubule organization in dendrites and for neuronal injury responses. The core nucleation protein, γTubulin (γTub), is localized to dendrite branch points in Drosophila sensory neurons by Wnt receptors and scaffolding proteins on endosomes, but whether Wnt ligands are important is unknown. Thyagarajan et al. find that Wnt secretion from epithelial cells was required for γTub localization to dendrite branch points. Using RNAi and mutant approaches, they showed that Wnt4 and wntD both position γTub. Moreover, injury-induced increases in neuronal microtubule dynamics required Wnt secretion from epithelial cells. Overexpression of Wnts in epithelial cells increased microtubule dynamics to the same extent as axon injury indicating surrounding cells have an instructive role in neuronal nucleation. To determine how Wnt ligands concentrate microtubule nucleation at dendrite branch points, the authors tested whether endocytosis is restricted to specific regions of dendrites. Markers of clathrin-mediated endocytosis localized to puncta at branch points. Behavior of these puncta was sensitive to inhibition of endocytosis suggesting they represented endocytic sites. Overall, the authors propose that the localization of Wnt endocytic sites to dendrite branch points results in the local generation of microtubule nucleating endosomes. The image shows class I sensory neurons (purple) in the context of the Drosophila larval body wall; epidermal cells that sit above the neurons are shown in green.
Image Credit: Pankajam Thyagarajan