Resistance to inhibitors of cholinesterase 3 (Ric-3) expression promotes selective protein associations with the human α7-nicotinic acetylcholine receptor interactome

Abstract: The α7-nicotinic acetylcholine receptor (α7-nAChR) is a ligand-gated ion channel widely expressed in vertebrates and is associated with numerous physiological functions. As transmembrane ion channels, α7-nAChRs need to be expressed on the surface of the plasma membrane to function. The rec...

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Autores principales: Mulcahy, Matthew J., Blattman, Sydney B., Barrantes, Francisco José, Lukas, Ronald J., Hawrot, Edward
Formato: Artículo
Lenguaje:Inglés
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8728
Aporte de:
id I33-R139123456789-8728
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic MEDICINA
CANALES IONICOS
RECEPTORES
MEMBRANAS CELULARES
PROTEINAS
spellingShingle MEDICINA
CANALES IONICOS
RECEPTORES
MEMBRANAS CELULARES
PROTEINAS
Mulcahy, Matthew J.
Blattman, Sydney B.
Barrantes, Francisco José
Lukas, Ronald J.
Hawrot, Edward
Resistance to inhibitors of cholinesterase 3 (Ric-3) expression promotes selective protein associations with the human α7-nicotinic acetylcholine receptor interactome
topic_facet MEDICINA
CANALES IONICOS
RECEPTORES
MEMBRANAS CELULARES
PROTEINAS
description Abstract: The α7-nicotinic acetylcholine receptor (α7-nAChR) is a ligand-gated ion channel widely expressed in vertebrates and is associated with numerous physiological functions. As transmembrane ion channels, α7-nAChRs need to be expressed on the surface of the plasma membrane to function. The receptor has been reported to associate with proteins involved with receptor biogenesis, modulation of receptor properties, as well as intracellular signaling cascades and some of these associated proteins may affect surface expression of α7-nAChRs. The putative chaperone resistance to inhibitors of cholinesterase 3 (Ric-3) has been reported to interact with, and enhance the surface expression of, α7-nAChRs. In this study, we identified proteins that associate with α7-nAChRs when Ric-3 is expressed. Using α-bungarotoxin (α-bgtx), we isolated and compared α7-nAChR-associated proteins from two stably transfected, human tumor-derived cell lines: SH-EP1-hα7 expressing human α7-nAChRs and the same cell line further transfected to express Ric-3, SH-EP1-hα7-Ric-3. Mass spectrometric analysis of peptides identified thirty-nine proteins that are associated with α7-nAChRs only when Ric-3 was expressed. Significantly, and consistent with reports of Ric-3 function in the literature, several of the identified proteins are involved in biological processes that may affect nAChR surface expression such as post-translational processing of proteins, protein trafficking, and protein transport. Additionally, proteins affecting the cell cycle, the cytoskeleton, stress responses, as well as cyclic AMP- and inositol triphosphate-dependent signaling cascades were identified. These results illuminate how α-bgtx may be used to isolate and identify α7-nAChRs as well as how the expression of chaperones such as Ric-3 can influence proteins associating with α7-nAChRs. These associating proteins may alter activities of α7-nAChRs to expand their functionally-relevant repertoire as well as to affect biogenesis and membrane trafficking of α7-nAChRs.
format Artículo
author Mulcahy, Matthew J.
Blattman, Sydney B.
Barrantes, Francisco José
Lukas, Ronald J.
Hawrot, Edward
author_facet Mulcahy, Matthew J.
Blattman, Sydney B.
Barrantes, Francisco José
Lukas, Ronald J.
Hawrot, Edward
author_sort Mulcahy, Matthew J.
title Resistance to inhibitors of cholinesterase 3 (Ric-3) expression promotes selective protein associations with the human α7-nicotinic acetylcholine receptor interactome
title_short Resistance to inhibitors of cholinesterase 3 (Ric-3) expression promotes selective protein associations with the human α7-nicotinic acetylcholine receptor interactome
title_full Resistance to inhibitors of cholinesterase 3 (Ric-3) expression promotes selective protein associations with the human α7-nicotinic acetylcholine receptor interactome
title_fullStr Resistance to inhibitors of cholinesterase 3 (Ric-3) expression promotes selective protein associations with the human α7-nicotinic acetylcholine receptor interactome
title_full_unstemmed Resistance to inhibitors of cholinesterase 3 (Ric-3) expression promotes selective protein associations with the human α7-nicotinic acetylcholine receptor interactome
title_sort resistance to inhibitors of cholinesterase 3 (ric-3) expression promotes selective protein associations with the human α7-nicotinic acetylcholine receptor interactome
publisher Public Library of Science
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8728
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