The GARP complex prevents sterol accumulation at the trans-Golgi network during dendrite remodeling

J Cell Biol. 2023 Jan 2;222(1):e202112108. doi: 10.1083/jcb.202112108. Epub 2022 Oct 14.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carrier Proteins
  • Dendrites* / metabolism
  • Drosophila
  • Drosophila Proteins
  • Golgi Apparatus / metabolism
  • Multiprotein Complexes* / metabolism
  • Receptors, Steroid
  • Sterols / metabolism
  • Vesicular Transport Proteins* / metabolism
  • trans-Golgi Network* / metabolism

Substances

  • Carrier Proteins
  • Drosophila Proteins
  • Multiprotein Complexes
  • Osbp protein, Drosophila
  • Receptors, Steroid
  • Sterols
  • Vesicular Transport Proteins
  • oxysterol binding protein
  • scat protein, Drosophila