Rab32 family proteins regulate autophagosomal components recycling

J Cell Biol. 2024 Mar 4;223(3):e202306040. doi: 10.1083/jcb.202306040. Epub 2024 Feb 7.

Abstract

In autophagy, autophagosomes deliver the lumenal contents to lysosomes for degradation via autophagosome-lysosome fusion. In contrast, autophagosome outer membrane components were recycled via autophagosomal components recycling (ACR), which is mediated by the recycler complex. The recycler complex, composed of SNX4, SNX5, and SNX17, cooperate with the dynein-dynactin complex to mediate ACR. However, how ACR is regulated remains unknown. Here, we found that Rab32 family proteins localize to autolysosomes and are required for ACR, rather than other autophagosomal or lysosomal Rab proteins. The GTPase activity of Rab32 family proteins, governed by their guanine nucleotide exchange factor and GTPase-activating protein, plays a key role in regulating ACR. This regulation occurs through the control of recycler complex formation, as well as the connection between the recycler-cargo and dynactin complex. Together, our study reveals an unidentified Rab32 family-dependent regulatory mechanism for ACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Autophagosomes* / metabolism
  • Dynactin Complex / metabolism
  • Dyneins* / metabolism
  • GTPase-Activating Proteins* / metabolism
  • Humans
  • Lysosomes
  • Sorting Nexins*
  • rab GTP-Binding Proteins* / metabolism

Substances

  • Dynactin Complex
  • Dyneins
  • GTPase-Activating Proteins
  • rab GTP-Binding Proteins
  • SNX4 protein, human
  • SNX5 protein, human
  • SNX17 protein, human
  • Sorting Nexins