Cargando…

ERAS Is Constitutively Expressed in the Tissues of Adult Horses and May Be a Key Player in Basal Autophagy

ERas is a new gene of the Ras family found in murine embryonic stem (ES) cells. Its human ortholog is not expressed in human ES cells. So far ERas gene has only been found to be expressed in the tissues of adult cynomolgus monkeys and cattle; however, information about ERAS expression or its potenti...

Descripción completa

Detalles Bibliográficos
Autores principales: De Falco, Francesca, Perillo, Antonella, Del Piero, Fabio, Del Prete, Chiara, Zizzo, Nicola, Marcus, Ioan, Roperto, Sante
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171053/
https://www.ncbi.nlm.nih.gov/pubmed/35685342
http://dx.doi.org/10.3389/fvets.2022.818294
_version_ 1784721576470511616
author De Falco, Francesca
Perillo, Antonella
Del Piero, Fabio
Del Prete, Chiara
Zizzo, Nicola
Marcus, Ioan
Roperto, Sante
author_facet De Falco, Francesca
Perillo, Antonella
Del Piero, Fabio
Del Prete, Chiara
Zizzo, Nicola
Marcus, Ioan
Roperto, Sante
author_sort De Falco, Francesca
collection PubMed
description ERas is a new gene of the Ras family found in murine embryonic stem (ES) cells. Its human ortholog is not expressed in human ES cells. So far ERas gene has only been found to be expressed in the tissues of adult cynomolgus monkeys and cattle; however, information about ERAS expression or its potential functions in equine tissues is lacking. This study was performed to investigate whether Eras is an equine functional gene and whether ERAS is expressed in the tissues of adult horses and determine its potential physiological role. Expression of the ERas gene was detected in all examined adult tissues, and the RT-PCR assay revealed ERAS transcripts. Protein expression was also detected by Western blot analysis. Quantitative real time RT-qPCR analysis revealed that different expression levels of ERAS transcripts were most highly expressed in the testis. Immunohistochemically, ERAS was found to be localized prevalently in the plasmatic membrane as well as cytoplasm of the cells. ERAS was a physical partner of activated PDGFβR leading to the AKT signaling. ERAS was found to interact with a network of proteins (BAG3, CHIP, Hsc70/Hsp70, HspB8, Synpo2, and p62) known to play a role in the chaperone-assisted selective autophagy (CASA), which is also known as BAG3-mediated selective macroautophagy, an adaptive mechanism to maintain cellular homeostasis. Furthermore, ERAS was found to interact with parkin. PINK1, BNIP3, laforin. All these proteins are known to play a role in parkin-dependent and -independent mitophagy. This is the first study demonstrating that Eras is a functional gene, and that ERAS is constitutively expressed in the tissues of adult horses. ERAS appears to play a physiological role in cellular proteostasis maintenance, thus mitigating the proteotoxicity of accumulated misfolded proteins and contributing to protection against disease. Finally, it is conceivable that activation of AKT pathway by PDGFRs promotes actin reorganization, directed cell movements, stimulation of cell growth.
format Online
Article
Text
id pubmed-9171053
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-91710532022-06-08 ERAS Is Constitutively Expressed in the Tissues of Adult Horses and May Be a Key Player in Basal Autophagy De Falco, Francesca Perillo, Antonella Del Piero, Fabio Del Prete, Chiara Zizzo, Nicola Marcus, Ioan Roperto, Sante Front Vet Sci Veterinary Science ERas is a new gene of the Ras family found in murine embryonic stem (ES) cells. Its human ortholog is not expressed in human ES cells. So far ERas gene has only been found to be expressed in the tissues of adult cynomolgus monkeys and cattle; however, information about ERAS expression or its potential functions in equine tissues is lacking. This study was performed to investigate whether Eras is an equine functional gene and whether ERAS is expressed in the tissues of adult horses and determine its potential physiological role. Expression of the ERas gene was detected in all examined adult tissues, and the RT-PCR assay revealed ERAS transcripts. Protein expression was also detected by Western blot analysis. Quantitative real time RT-qPCR analysis revealed that different expression levels of ERAS transcripts were most highly expressed in the testis. Immunohistochemically, ERAS was found to be localized prevalently in the plasmatic membrane as well as cytoplasm of the cells. ERAS was a physical partner of activated PDGFβR leading to the AKT signaling. ERAS was found to interact with a network of proteins (BAG3, CHIP, Hsc70/Hsp70, HspB8, Synpo2, and p62) known to play a role in the chaperone-assisted selective autophagy (CASA), which is also known as BAG3-mediated selective macroautophagy, an adaptive mechanism to maintain cellular homeostasis. Furthermore, ERAS was found to interact with parkin. PINK1, BNIP3, laforin. All these proteins are known to play a role in parkin-dependent and -independent mitophagy. This is the first study demonstrating that Eras is a functional gene, and that ERAS is constitutively expressed in the tissues of adult horses. ERAS appears to play a physiological role in cellular proteostasis maintenance, thus mitigating the proteotoxicity of accumulated misfolded proteins and contributing to protection against disease. Finally, it is conceivable that activation of AKT pathway by PDGFRs promotes actin reorganization, directed cell movements, stimulation of cell growth. Frontiers Media S.A. 2022-05-24 /pmc/articles/PMC9171053/ /pubmed/35685342 http://dx.doi.org/10.3389/fvets.2022.818294 Text en Copyright © 2022 De Falco, Perillo, Del Piero, Del Prete, Zizzo, Marcus and Roperto. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
De Falco, Francesca
Perillo, Antonella
Del Piero, Fabio
Del Prete, Chiara
Zizzo, Nicola
Marcus, Ioan
Roperto, Sante
ERAS Is Constitutively Expressed in the Tissues of Adult Horses and May Be a Key Player in Basal Autophagy
title ERAS Is Constitutively Expressed in the Tissues of Adult Horses and May Be a Key Player in Basal Autophagy
title_full ERAS Is Constitutively Expressed in the Tissues of Adult Horses and May Be a Key Player in Basal Autophagy
title_fullStr ERAS Is Constitutively Expressed in the Tissues of Adult Horses and May Be a Key Player in Basal Autophagy
title_full_unstemmed ERAS Is Constitutively Expressed in the Tissues of Adult Horses and May Be a Key Player in Basal Autophagy
title_short ERAS Is Constitutively Expressed in the Tissues of Adult Horses and May Be a Key Player in Basal Autophagy
title_sort eras is constitutively expressed in the tissues of adult horses and may be a key player in basal autophagy
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171053/
https://www.ncbi.nlm.nih.gov/pubmed/35685342
http://dx.doi.org/10.3389/fvets.2022.818294
work_keys_str_mv AT defalcofrancesca erasisconstitutivelyexpressedinthetissuesofadulthorsesandmaybeakeyplayerinbasalautophagy
AT perilloantonella erasisconstitutivelyexpressedinthetissuesofadulthorsesandmaybeakeyplayerinbasalautophagy
AT delpierofabio erasisconstitutivelyexpressedinthetissuesofadulthorsesandmaybeakeyplayerinbasalautophagy
AT delpretechiara erasisconstitutivelyexpressedinthetissuesofadulthorsesandmaybeakeyplayerinbasalautophagy
AT zizzonicola erasisconstitutivelyexpressedinthetissuesofadulthorsesandmaybeakeyplayerinbasalautophagy
AT marcusioan erasisconstitutivelyexpressedinthetissuesofadulthorsesandmaybeakeyplayerinbasalautophagy
AT ropertosante erasisconstitutivelyexpressedinthetissuesofadulthorsesandmaybeakeyplayerinbasalautophagy