Descamps, Estelle;
(2020)
Investigation of the function of the PTPMEG2 phosphatase in mammalian autophagy.
Masters thesis (M.Phil), UCL (University College London).
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Abstract
Autophagy is a catabolic process that enables cells to engulf cytosolic components into a double-membrane vesicle called “autophagosome” to send them for lysosomal degradation. Autophagy occurs at a basal level to maintain cellular homeostasis but is dramatically induced by various stresses such as amino acid starvation to allow cells to generate new building blocks. The autophagic response is mediated by many different actors, most of them from the ATG proteins family. Among those, ATG9A is particularly interesting since it is the only transmembrane protein required for autophagy and its function remains unknown. ATG9A localises on vesicles and tubular structures that seem to make brief interactions with the forming autophagosomes without completely fusing with them. Therefore, ATG9A is thought to promote the delivery of proteins or lipids to fuel the growth of nascent autophagosomes. Proteomic analysis of immunoisolated ATG9A vesicles revealed the presence of PTPMEG2 on ATG9A-positive membranes, a tyrosine phosphatase with no previously described role in autophagy. In order to understand why PTPMEG2 is found on ATG9A-positive structures, I first assessed the impact of PTPMEG2 on the autophagic flux. However, the analysis of LC3 lipidation and of LC3 spots formation did not reveal any defect in the absence of PTPMEG2. Afterwards, I investigated the relationship between PTPMEG2 and ATG9A. My results suggest that the two proteins interact and that the localization of ATG9A is altered in the absence of PTPMEG2. As this phenotype is also observed upon loss of ARFIP2, another protein found on ATG9A vesicles, I then decided to explore the relationship between PTPMEG2 and ARFIP2 and confirmed that they interact with each other. Finally, I propose here a hypothetical model that integrates my data. However, more experiments are needed to better understand the possible interplay between ATG9A, PTPMEG2 and ARFIP2 in the distribution of ATG9A vesicles during autophagy.
| Type: | Thesis (Masters) |
|---|---|
| Qualification: | M.Phil |
| Title: | Investigation of the function of the PTPMEG2 phosphatase in mammalian autophagy |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10110905 |
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