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Loss of the essential autophagy regulators FIP200 or Atg5 leads to distinct effects on focal adhesion composition and organisation

Loss of the essential autophagy regulators FIP200 or Atg5 leads to distinct effects on focal adhesion composition and organisation
Loss of the essential autophagy regulators FIP200 or Atg5 leads to distinct effects on focal adhesion composition and organisation
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 signalling 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 organisation, as well as signalling 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, characterised 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 reorganisation and their exhibits colocalisation of autophagosomes with focal adhesion cargo. Interestingly, FIP200 localises 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 In review and impacts on focal adhesion dynamics associated with cell motility.
focal adhesion kinase, SRC, cell adhesion, autophagy, actin cytoskeleton
2296-634X
Assar, Emelia Arezo
95c06484-59ca-4cfb-a818-4d4ad7d0ea77
Tumbarello, David A
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2
Assar, Emelia Arezo
95c06484-59ca-4cfb-a818-4d4ad7d0ea77
Tumbarello, David A
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2

Assar, Emelia Arezo and Tumbarello, David A (2020) Loss of the essential autophagy regulators FIP200 or Atg5 leads to distinct effects on focal adhesion composition and organisation. Frontiers in Cell and Developmental Biology. (In Press)

Record type: Article

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 signalling 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 organisation, as well as signalling 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, characterised 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 reorganisation and their exhibits colocalisation of autophagosomes with focal adhesion cargo. Interestingly, FIP200 localises 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 In review and impacts on focal adhesion dynamics associated with cell motility.

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More information

Accepted/In Press date: 15 July 2020
Keywords: focal adhesion kinase, SRC, cell adhesion, autophagy, actin cytoskeleton

Identifiers

Local EPrints ID: 442534
URI: http://eprints.soton.ac.uk/id/eprint/442534
ISSN: 2296-634X
PURE UUID: f74dc193-02e8-4fec-b6a8-1140125cf3c2
ORCID for David A Tumbarello: ORCID iD orcid.org/0000-0002-5169-0561

Catalogue record

Date deposited: 17 Jul 2020 16:31
Last modified: 07 Oct 2020 02:05

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Contributors

Author: Emelia Arezo Assar

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