SNX18 regulates ATG9A trafficking from recycling endosomes by recruiting Dynamin-2

EMBO Rep. 2018 Apr;19(4):e44837. doi: 10.15252/embr.201744837. Epub 2018 Feb 7.

Abstract

Trafficking of mammalian ATG9A between the Golgi apparatus, endosomes and peripheral ATG9A compartments is important for autophagosome biogenesis. Here, we show that the membrane remodelling protein SNX18, previously identified as a positive regulator of autophagy, regulates ATG9A trafficking from recycling endosomes. ATG9A is recruited to SNX18-induced tubules generated from recycling endosomes and accumulates in juxtanuclear recycling endosomes in cells lacking SNX18. Binding of SNX18 to Dynamin-2 is important for ATG9A trafficking from recycling endosomes and for formation of ATG16L1- and WIPI2-positive autophagosome precursor membranes. We propose a model where upon autophagy induction, SNX18 recruits Dynamin-2 to induce budding of ATG9A and ATG16L1 containing membranes from recycling endosomes that traffic to sites of autophagosome formation.

Keywords: ATG9; SNX18; autophagy; dynamin; recycling endosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy
  • Autophagy-Related Proteins / metabolism*
  • Carrier Proteins / metabolism
  • Dynamin II / metabolism*
  • Endosomes / metabolism*
  • GTPase-Activating Proteins / metabolism
  • Humans
  • Intracellular Membranes / metabolism
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Phosphate-Binding Proteins
  • Protein Binding
  • Protein Transport
  • Sorting Nexins / metabolism*
  • Vesicular Transport Proteins / metabolism*

Substances

  • ATG9A protein, human
  • Autophagy-Related Proteins
  • Carrier Proteins
  • GTPase-Activating Proteins
  • Membrane Proteins
  • Phosphate-Binding Proteins
  • SNX18 protein, human
  • Sorting Nexins
  • TBC1D14 protein, human
  • Vesicular Transport Proteins
  • WIPI2 protein, human
  • Dynamin II