Next Article in Journal
B Cells and B Cell Blasts Withstand Cryopreservation While Retaining Their Functionality for Producing Antibody
Previous Article in Journal
Human-Induced Pluripotent Stem Cell Technology and Cardiomyocyte Generation: Progress and Clinical Applications
Previous Article in Special Issue
Autophagy in Age-Associated Neurodegeneration
Article Menu
Issue 6 (June) cover image

Export Article

Open AccessArticle
Cells 2018, 7(6), 49; https://doi.org/10.3390/cells7060049

Novel Modulators of Proteostasis: RNAi Screen of Chromosome I in a Heat Stress Paradigm in C. elegans

Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55099 Mainz, Germany
*
Author to whom correspondence should be addressed.
Received: 26 March 2018 / Revised: 17 May 2018 / Accepted: 24 May 2018 / Published: 26 May 2018
(This article belongs to the Special Issue Autophagy in Age-Related Human Diseases)
View Full-Text   |   Download PDF [1126 KB, uploaded 26 May 2018]   |  

Abstract

Proteostasis is of vital importance for cellular function and it is challenged upon exposure to acute or chronic insults during neurodegeneration and aging. The proteostasis network is relevant for the maintenance of proteome integrity and mainly comprises molecular chaperones and two degradation pathways, namely, autophagy and the ubiquitin proteasome system. This network is characterized by an impressive functional interrelation and complexity, and occasionally novel factors are discovered that modulate proteostasis. Here, we present an RNAi screen in C. elegans, which aimed to identify modulators of proteostasis in a heat stress paradigm. The screen comprised genes that are located on chromosome I of the nematode and has identified 185 genetic modifiers, whose knockdown has enhanced the misfolding of a reporter protein upon temperature increase. Subsequently, we evaluated the effect of a distinct number of the identified candidates in an additional C. elegans model strain, which expresses the aggregation-prone PolyQ35::YFP protein. Moreover, we annotated the human orthologs of the identified proteins and analyzed their enrichment in functional clusters and, as appropriate, their association with human neuropathologies. The achieved data collection includes several factors that have already been functionally associated with the proteostasis network, which highlights the potential of this heat stress-based proteostasis screen in order to detect novel modulators of proteome integrity. View Full-Text
Keywords: C. elegans; RNAi screen; proteostasis; proteostasis network; autophagy; UPS; chaperone; neurodegeneration C. elegans; RNAi screen; proteostasis; proteostasis network; autophagy; UPS; chaperone; neurodegeneration
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Kern, A.; Spang, N.; Huesmann, H.; Behl, C. Novel Modulators of Proteostasis: RNAi Screen of Chromosome I in a Heat Stress Paradigm in C. elegans. Cells 2018, 7, 49.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top