![]() Both the secretory ( Wang et al., 2017 Wang et al., 2018) and endocytic ( Kanamori et al., 2015 Krämer et al., 2019) pathways also play important roles during developmental pruning and remodeling of dendrites. Endocytosis and recycling pathways are also required for growth factor-mediated branching of dendrites ( Lazo et al., 2013) and axons ( Ascano et al., 2009). Secretory vesicles are essential sources of membrane for neurite outgrowth ( Vega and Hsu, 2001), and dendrite development is particularly sensitive to inhibition of secretory trafficking ( Ye et al., 2007). Membrane trafficking pathways are essential to establishing and sculpting neuronal morphology during development ( Winkle and Gupton, 2016). Neurons initially establish their architectures during embryogenesis, which is followed by an extended post-embryonic period during which excess branches are pruned and remodeled into their mature states ( Stiles and Jernigan, 2010). Proper wiring of the nervous system depends on the development and maintenance of complex-polarized neuronal morphologies. These findings distinguish the GARP and EARP complexes in neurodevelopment and implicate vesicle trafficking and lipid transfer pathways in dendrite morphogenesis. Overexpression of oxysterol binding protein (Osbp) or knockdown of the PI4K four wheel drive (fwd) exacerbates the Vps54 KO/KO phenotype, whereas eliminating one allele of Osbp rescues it, suggesting that excess sterol accumulation at the TGN is, in part, responsible for inhibiting dendrite regrowth. Having found that sterol accumulates at the trans-Golgi network (TGN) in Vps54 KO/KO neurons, we investigated genes that regulate sterols and related lipids at the TGN. In Drosophila, we find that both complexes are required for dendrite morphogenesis during developmental remodeling of multidendritic class IV da (c4da) neurons. Both complexes contain the Vps51, Vps52, and Vps53 proteins, and a complex-specific protein: Vps54 in GARP and Vps50 in EARP. The GARP and EARP complexes are conserved tethers that regulate vesicle trafficking in the secretory and endolysosomal pathways, respectively. Membrane trafficking is essential for sculpting neuronal morphology.
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