Reticulon1-C modulates protein disulphide isomerase function

Endoplasmic reticulum (ER) is the primary site for the synthesis and folding of secreted and membrane-bound proteins. Accumulation of unfolded and misfolded proteins in ER underlies a wide range of human neurodegenerative disorders. Hence, molecules regulating the ER stress response represent potent...

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Main Authors:	Bernardoni, P, Fazi, B, Costanzi, A, Nardacci, R, Montagna, C, Filomeni, G, Ciriolo, M R, Piacentini, M, Di Sano, F
Format:	Online
Language:	English
Published:	Nature Publishing Group 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641336/

id	pubmed-3641336
recordtype	oai_dc
spelling	pubmed-36413362013-05-02 Reticulon1-C modulates protein disulphide isomerase function Bernardoni, P Fazi, B Costanzi, A Nardacci, R Montagna, C Filomeni, G Ciriolo, M R Piacentini, M Di Sano, F Original Article Endoplasmic reticulum (ER) is the primary site for the synthesis and folding of secreted and membrane-bound proteins. Accumulation of unfolded and misfolded proteins in ER underlies a wide range of human neurodegenerative disorders. Hence, molecules regulating the ER stress response represent potential candidates as drug targets for tackling these diseases. Protein disulphide isomerase (PDI) is a chaperone involved in ER stress pathway, its activity being an important cellular defense against protein misfolding. Here, we demonstrate that human neuroblastoma SH-SY5Y cells overexpressing the reticulon protein 1-C (RTN1-C) reticulon family member show a PDI punctuate subcellular distribution identified as ER vesicles. This represents an event associated with a significant increase of PDI enzymatic activity. We provide evidence that the modulation of PDI localization and activity does not only rely upon ER stress induction or upregulation of its synthesis, but tightly correlates to an alteration in its nitrosylation status. By using different RTN1-C mutants, we demonstrate that the observed effects depend on RTN1-C N-terminal region and on the integrity of the microtubule network. Overall, our results indicate that RTN1-C induces PDI redistribution in ER vesicles, and concomitantly modulates its activity by decreasing the levels of its S-nitrosylated form. Thus RTN1-C represents a promising candidate to modulate PDI function. Nature Publishing Group 2013-04 2013-04-04 /pmc/articles/PMC3641336/ /pubmed/23559015 http://dx.doi.org/10.1038/cddis.2013.113 Text en Copyright © 2013 Macmillan Publishers Limited 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/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Bernardoni, P Fazi, B Costanzi, A Nardacci, R Montagna, C Filomeni, G Ciriolo, M R Piacentini, M Di Sano, F
spellingShingle	Bernardoni, P Fazi, B Costanzi, A Nardacci, R Montagna, C Filomeni, G Ciriolo, M R Piacentini, M Di Sano, F Reticulon1-C modulates protein disulphide isomerase function
author_facet	Bernardoni, P Fazi, B Costanzi, A Nardacci, R Montagna, C Filomeni, G Ciriolo, M R Piacentini, M Di Sano, F
author_sort	Bernardoni, P
title	Reticulon1-C modulates protein disulphide isomerase function
title_short	Reticulon1-C modulates protein disulphide isomerase function
title_full	Reticulon1-C modulates protein disulphide isomerase function
title_fullStr	Reticulon1-C modulates protein disulphide isomerase function
title_full_unstemmed	Reticulon1-C modulates protein disulphide isomerase function
title_sort	reticulon1-c modulates protein disulphide isomerase function
description	Endoplasmic reticulum (ER) is the primary site for the synthesis and folding of secreted and membrane-bound proteins. Accumulation of unfolded and misfolded proteins in ER underlies a wide range of human neurodegenerative disorders. Hence, molecules regulating the ER stress response represent potential candidates as drug targets for tackling these diseases. Protein disulphide isomerase (PDI) is a chaperone involved in ER stress pathway, its activity being an important cellular defense against protein misfolding. Here, we demonstrate that human neuroblastoma SH-SY5Y cells overexpressing the reticulon protein 1-C (RTN1-C) reticulon family member show a PDI punctuate subcellular distribution identified as ER vesicles. This represents an event associated with a significant increase of PDI enzymatic activity. We provide evidence that the modulation of PDI localization and activity does not only rely upon ER stress induction or upregulation of its synthesis, but tightly correlates to an alteration in its nitrosylation status. By using different RTN1-C mutants, we demonstrate that the observed effects depend on RTN1-C N-terminal region and on the integrity of the microtubule network. Overall, our results indicate that RTN1-C induces PDI redistribution in ER vesicles, and concomitantly modulates its activity by decreasing the levels of its S-nitrosylated form. Thus RTN1-C represents a promising candidate to modulate PDI function.
publisher	Nature Publishing Group
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641336/
_version_	1611974203111636992

Reticulon1-C modulates protein disulphide isomerase function

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