The core autophagy protein ATG9A controls dynamics of cell protrusions and directed migration

J Cell Biol. 2022 Mar 7;221(3):e202106014. doi: 10.1083/jcb.202106014. Epub 2022 Feb 18.

Abstract

Chemotactic migration is a fundamental cellular behavior relying on the coordinated flux of lipids and cargo proteins toward the leading edge. We found here that the core autophagy protein ATG9A plays a critical role in the chemotactic migration of several human cell lines, including highly invasive glioma cells. Depletion of ATG9A protein altered the formation of large and persistent filamentous actin (F-actin)-rich lamellipodia that normally drive directional migration. Using live-cell TIRF microscopy, we demonstrated that ATG9A-positive vesicles are targeted toward the migration front of polarized cells, where their exocytosis correlates with protrusive activity. Finally, we found that ATG9A was critical for efficient delivery of β1 integrin to the leading edge and normal adhesion dynamics. Collectively, our data uncover a new function for ATG9A protein and indicate that ATG9A-positive vesicles are mobilized during chemotactic stimulation to facilitate expansion of the lamellipodium and its anchorage to the extracellular matrix.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Autophagy*
  • Autophagy-Related Proteins / metabolism*
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Surface Extensions / metabolism*
  • Chemotaxis
  • Exocytosis
  • Green Fluorescent Proteins
  • Humans
  • Integrin beta1 / metabolism
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / metabolism*
  • Pseudopodia / metabolism
  • Reproducibility of Results
  • Vesicular Transport Proteins / metabolism*

Substances

  • Actins
  • ATG9A protein, human
  • Autophagy-Related Proteins
  • Integrin beta1
  • Membrane Glycoproteins
  • Membrane Proteins
  • PHluorin
  • TGOLN2 protein, human
  • Vesicular Transport Proteins
  • Green Fluorescent Proteins