| Autor: |
Mulcahy MJ; Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island, United States of America., Blattman SB; Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island, United States of America., Barrantes FJ; Laboratory of Molecular Neurobiology, Institute of Biomedical Research, UCA-CONICET, Buenos Aires, Argentina., Lukas RJ; Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, United States of America., Hawrot E; Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island, United States of America. |
| Jazyk: |
angličtina |
| Zdroj: |
PloS one [PLoS One] 2015 Aug 10; Vol. 10 (8), pp. e0134409. Date of Electronic Publication: 2015 Aug 10 (Print Publication: 2015). |
| DOI: |
10.1371/journal.pone.0134409 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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