RAB37 interacts directly with ATG5 and promotes autophagosome formation via regulating ATG5-12-16 complex assembly

Cell Death Differ. 2018 May;25(5):918-934. doi: 10.1038/s41418-017-0023-1. Epub 2017 Dec 11.


Intracellular membrane trafficking is essential for eukaryotic cell existence. Here, we show that RAB37 activation through GTP binding recruits ATG5-12 to isolation membrane and promotes autophagosome formation through the ATG5-ATG12-ATG16L1 complex. RAB37 is localized on the isolation membrane. It can bind directly with ATG5 and promotes formation of the ATG5-12-16 complex. Mutation analysis reveals that GTP-bound RAB37 exhibits an enhanced interaction with ATG5-12 and GDP-stabilised mutation impairs the interaction. RAB37 promotes ATG5-12 interaction with ATG16L1, thus facilitates lipidation of LC3B in a GTP-dependent manner to enhance autophagy. Notably, ablation of RAB37 expression affects the complex formation and decreases autophagy, whereas forced RAB37 expression promotes autophagy and also suppresses cell proliferation. Our results demonstrate a role of RAB37 in autophagosome formation through a molecular connection of RAB37, ATG5-12, ATG16L1 up to LC3B, suggesting an organiser role of RAB37 during autophagosomal membrane biogenesis. These findings have broad implications for understanding the role of RAB vesicle transport in autophagy and cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagosomes / metabolism*
  • Autophagy*
  • Autophagy-Related Protein 5 / genetics
  • Autophagy-Related Protein 5 / metabolism*
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism
  • COS Cells
  • Chlorocebus aethiops
  • HeLa Cells
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*


  • ATG16L1 protein, human
  • ATG5 protein, human
  • Autophagy-Related Protein 5
  • Autophagy-Related Proteins
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • Rab37 protein, human
  • rab GTP-Binding Proteins