Autophagy modulates cell migration and β1 integrin membrane recycling

Cell Cycle. 2013 Oct 15;12(20):3317-28. doi: 10.4161/cc.26298. Epub 2013 Sep 9.

Abstract

Cell migration is dependent on a series of integrated cellular events including the membrane recycling of the extracellular matrix receptor integrins. In this paper, we investigate the role of autophagy in regulating cell migration. In a wound-healing assay, we observed that autophagy was reduced in cells at the leading edge than in cells located rearward. These differences in autophagy were correlated with the robustness of MTOR activity. The spatial difference in the accumulation of autophagic structures was not detected in rapamycin-treated cells, which had less migration capacity than untreated cells. In contrast, the knockdown of the autophagic protein ATG7 stimulated cell migration of HeLa cells. Accordingly, atg3(-/-) and atg5(-/-) MEFs have greater cell migration properties than their wild-type counterparts. Stimulation of autophagy increased the co-localization of β1 integrin-containing vesicles with LC3-stained autophagic vacuoles. Moreover, inhibition of autophagy slowed down the lysosomal degradation of internalized β1 integrins and promoted its membrane recycling. From these findings, we conclude that autophagy regulates cell migration, a central mechanism in cell development, angiogenesis, and tumor progression, by mitigating the cell surface expression of β1 integrins.

Keywords: MTOR; cell migration; endocytosis; integrins; lysosomes; macroautophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Autophagy-Related Protein 7
  • Cell Adhesion
  • Cell Membrane / metabolism*
  • Cell Movement*
  • Endocytosis*
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Humans
  • Integrin beta1 / metabolism*
  • Lysosomes / metabolism
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Phagosomes / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • Ubiquitin-Activating Enzymes / metabolism

Substances

  • Integrin beta1
  • Microtubule-Associated Proteins
  • light chain 3, human
  • Green Fluorescent Proteins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Atg7 protein, human
  • Autophagy-Related Protein 7
  • Ubiquitin-Activating Enzymes