The GARP complex prevents sterol accumulation at the trans-Golgi network during dendrite remodeling
| Autor: | Caitlin E. O’Brien, Susan H. Younger, Lily Yeh Jan, Yuh Nung Jan |
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| Rok vydání: | 2022 |
| Předmět: |
Receptors
Steroid 1.1 Normal biological development and functioning Neurosciences Vesicular Transport Proteins Golgi Apparatus Dendrites Cell Biology Biological Sciences Medical and Health Sciences Sterols Underpinning research Multiprotein Complexes Receptors Animals Drosophila Proteins Drosophila Generic health relevance Carrier Proteins Steroid Developmental Biology trans-Golgi Network |
| Zdroj: | The Journal of cell biology, vol 222, iss 1 |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Membrane trafficking is essential for sculpting neuronal morphology. The GARP and EARP complexes are conserved tethers that regulate vesicle trafficking in the secretory and endolysosomal pathways, respectively. Both complexes contain the Vps51, Vps52, and Vps53 proteins, and a complex-specific protein: Vps54 in GARP and Vps50 in EARP. In Drosophila, we find that both complexes are required for dendrite morphogenesis during developmental remodeling of multidendritic class IV da (c4da) neurons. Having found that sterol accumulates at the trans-Golgi network (TGN) in Vps54KO/KO neurons, we investigated genes that regulate sterols and related lipids at the TGN. Overexpression of oxysterol binding protein (Osbp) or knockdown of the PI4K four wheel drive (fwd) exacerbates the Vps54KO/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. These findings distinguish the GARP and EARP complexes in neurodevelopment and implicate vesicle trafficking and lipid transfer pathways in dendrite morphogenesis. |
| Databáze: | OpenAIRE |
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