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The VMP1-Beclin 1 interaction regulates autophagy induction

The Vacuole Membrane Protein 1 -VMP1- is a pancreatitis-associated transmembrane protein whose expression triggers autophagy in several human diseases. In the current study, we unveil the mechanism through which this protein induces autophagosome formation in mammalian cells. We show that VMP1 autop...

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Autores principales: Molejon, Maria I., Ropolo, Alejandro, Re, Andrea Lo, Boggio, Veronica, Vaccaro, Maria I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542764/
https://www.ncbi.nlm.nih.gov/pubmed/23316280
http://dx.doi.org/10.1038/srep01055
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author Molejon, Maria I.
Ropolo, Alejandro
Re, Andrea Lo
Boggio, Veronica
Vaccaro, Maria I.
author_facet Molejon, Maria I.
Ropolo, Alejandro
Re, Andrea Lo
Boggio, Veronica
Vaccaro, Maria I.
author_sort Molejon, Maria I.
collection PubMed
description The Vacuole Membrane Protein 1 -VMP1- is a pancreatitis-associated transmembrane protein whose expression triggers autophagy in several human diseases. In the current study, we unveil the mechanism through which this protein induces autophagosome formation in mammalian cells. We show that VMP1 autophagy-related function requires its 20-aminoacid C-terminus hydrophilic domain (VMP1-AtgD). This is achieved through its direct binding to the BH3 motif of Beclin 1 leading to the formation of a complex with the Class III phosphatidylinositol-3 kinase (PI3K) hVps34, a key positive regulator of autophagy, at the site where autophagosomes are generated. This interaction also concomitantly promotes the dissociation of Bcl-2, an autophagy inhibitor, from Beclin 1. Moreover, we show that the VMP1-Beclin 1-hVps34 complex favors the association of Atg16L1 and LC3 with the autophagosomal membranes. Collectively, these findings reveal that VMP1 expression recruits and activates the Class III PI3K complex at the site of autophagosome formation during mammalian autophagy.
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spelling pubmed-35427642013-01-11 The VMP1-Beclin 1 interaction regulates autophagy induction Molejon, Maria I. Ropolo, Alejandro Re, Andrea Lo Boggio, Veronica Vaccaro, Maria I. Sci Rep Article The Vacuole Membrane Protein 1 -VMP1- is a pancreatitis-associated transmembrane protein whose expression triggers autophagy in several human diseases. In the current study, we unveil the mechanism through which this protein induces autophagosome formation in mammalian cells. We show that VMP1 autophagy-related function requires its 20-aminoacid C-terminus hydrophilic domain (VMP1-AtgD). This is achieved through its direct binding to the BH3 motif of Beclin 1 leading to the formation of a complex with the Class III phosphatidylinositol-3 kinase (PI3K) hVps34, a key positive regulator of autophagy, at the site where autophagosomes are generated. This interaction also concomitantly promotes the dissociation of Bcl-2, an autophagy inhibitor, from Beclin 1. Moreover, we show that the VMP1-Beclin 1-hVps34 complex favors the association of Atg16L1 and LC3 with the autophagosomal membranes. Collectively, these findings reveal that VMP1 expression recruits and activates the Class III PI3K complex at the site of autophagosome formation during mammalian autophagy. Nature Publishing Group 2013-01-11 /pmc/articles/PMC3542764/ /pubmed/23316280 http://dx.doi.org/10.1038/srep01055 Text en Copyright © 2013, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Article
Molejon, Maria I.
Ropolo, Alejandro
Re, Andrea Lo
Boggio, Veronica
Vaccaro, Maria I.
The VMP1-Beclin 1 interaction regulates autophagy induction
title The VMP1-Beclin 1 interaction regulates autophagy induction
title_full The VMP1-Beclin 1 interaction regulates autophagy induction
title_fullStr The VMP1-Beclin 1 interaction regulates autophagy induction
title_full_unstemmed The VMP1-Beclin 1 interaction regulates autophagy induction
title_short The VMP1-Beclin 1 interaction regulates autophagy induction
title_sort vmp1-beclin 1 interaction regulates autophagy induction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542764/
https://www.ncbi.nlm.nih.gov/pubmed/23316280
http://dx.doi.org/10.1038/srep01055
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