In Planta Preliminary Screening of ER Glycoprotein Folding Quality Control (ERQC) Modulators.pdf (3.83 MB)
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In Planta Preliminary Screening of ER Glycoprotein Folding Quality Control (ERQC) Modulators.

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journal contribution
posted on 01.07.2019, 11:11 by L Marti, A Lia, I-B Reca, P Roversi, A Santino, N Zitzmann
Small molecule modulators of the Endoplasmic Reticulum glycoprotein folding quality control (ERQC) machinery have broad-spectrum antiviral activity against a number of enveloped viruses and have the potential to rescue secretion of misfolded but active glycoproteins in rare diseases. In vivo assays of candidate inhibitors in mammals are expensive and cannot be afforded at the preliminary stages of drug development programs. The strong conservation of the ERQC machinery across eukaryotes makes transgenic plants an attractive system for low-cost, easy and fast proof-of-concept screening of candidate ERQC inhibitors. The Arabidopsis thaliana immune response is mediated by glycoproteins, the folding of which is controlled by ERQC. We have used the plant response to bacterial peptides as a means of assaying an ERQC inhibitor in vivo. We show that the treatment of the plant with the iminosugar NB-DNJ, which is a known ER α-glucosidase inhibitor in mammals, influences the immune response of the plant to the bacterial peptide elf18 but not to the flagellin-derived flg22 peptide. In the NB-DNJ-treated plant, the responses to elf18 and flg22 treatments closely follow the ones observed for the ER α-glucosidase II impaired plant, At psl5-1. We propose Arabidopsis thaliana as a promising platform for the development of low-cost proof-of-concept in vivo ERQC modulation.

Funding

Arabidopsis thaliana psl5-1 mutants (in the Col-0 background) were kindly provided by Yusuke Saijo (Department of Plant Microbe Interactions, Max Planck Institute, Germany). N.Z. is a Fellow of Merton College, Oxford. PR is the recipient of a LISCB Wellcome Trust ISSF award, grant reference 204801/Z/16/Z.

History

Citation

International Journal of Molecular Sciences, 2018, 19 (7)

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Molecular & Cell Biology

Version

VoR (Version of Record)

Published in

International Journal of Molecular Sciences

Publisher

MDPI

eissn

1422-0067

Acceptance date

19/07/2018

Copyright date

2018

Available date

01/07/2019

Publisher version

https://www.mdpi.com/1422-0067/19/7/2135

Language

en