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Assar EA, Tumbarello DA. Loss of the Essential Autophagy Regulators FIP200 or Atg5 Leads to Distinct Effects on Focal Adhesion Composition and Organization. Front Cell Dev Biol. 2020;8:733doi: 10.3389/fcell.2020.00733.
Assar, E. A., & Tumbarello, D. A. (2020). Loss of the Essential Autophagy Regulators FIP200 or Atg5 Leads to Distinct Effects on Focal Adhesion Composition and Organization. Frontiers in cell and developmental biology, 8733. https://doi.org/10.3389/fcell.2020.00733
Assar, Emelia A, and Tumbarello, David A. "Loss of the Essential Autophagy Regulators FIP200 or Atg5 Leads to Distinct Effects on Focal Adhesion Composition and Organization." Frontiers in cell and developmental biology vol. 8 (2020): 733. doi: https://doi.org/10.3389/fcell.2020.00733
Assar EA, Tumbarello DA. Loss of the Essential Autophagy Regulators FIP200 or Atg5 Leads to Distinct Effects on Focal Adhesion Composition and Organization. Front Cell Dev Biol. 2020 Aug 04;8:733. doi: 10.3389/fcell.2020.00733. eCollection 2020. PMID: 32850845; PMCID: PMC7417463.
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Front Cell Dev Biol. 2020 Aug 04;8:733. doi: 10.3389/fcell.2020.00733. eCollection 2020.

Loss of the Essential Autophagy Regulators FIP200 or Atg5 Leads to Distinct Effects on Focal Adhesion Composition and Organization.

Frontiers in cell and developmental biology

Emelia A Assar, David A Tumbarello

Affiliations

  1. Biological Sciences, University of Southampton, Southampton, United Kingdom.

PMID: 32850845 PMCID: PMC7417463 DOI: 10.3389/fcell.2020.00733

Abstract

Autophagy is an essential catabolic intracellular pathway that maintains homeostasis by degrading long-lived proteins, damaged organelles, and provides an energy source during nutrient starvation. It is now understood that autophagy has discrete functions as a selective lysosomal degradation pathway targeting large cytosolic structural and signaling complexes to influence cell motility and adhesion. We provide evidence suggesting the primary autophagy regulators Atg5 and FIP200 both play a role in cell motility and extracellular matrix adhesion. However, their loss of function has a differential impact on focal adhesion composition and organization, as well as signaling in response to fibronectin induced cell spreading. This differential impact on focal adhesions is illustrated by smaller focal adhesion complexes and a decrease in FAK, paxillin, and vinculin expression associated with FIP200 loss of function. In contrast, Atg5 loss of function results in production of large and stable focal adhesions, characterized by their retention of phosphorylated FAK and Src, which correlates with increased vinculin and FAK protein expression. Importantly, autophagy is upregulated during processes associated with focal adhesion reorganization and their exhibits colocalization of autophagosomes with focal adhesion cargo. Interestingly, FIP200 localizes to vinculin-rich focal adhesions and its loss negatively regulates FAK phosphorylation. These data collectively suggest FIP200 and Atg5 may have both autophagy-dependent and -independent functions that provide distinct mechanisms and impacts on focal adhesion dynamics associated with cell motility.

Copyright © 2020 Assar and Tumbarello.

Keywords: Src; actin cytoskeleton; autophagy; cell adhesion; focal adhesion kinase

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