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A pro-cathepsin L mutant is a luminal substrate for endoplasmic-reticulum-associated degradation in C. elegans

Miedel, MT and Graf, NJ and Stephen, KE and Long, OS and Pak, SC and Perlmutter, DH and Silverman, GA and Luke, CJ (2012) A pro-cathepsin L mutant is a luminal substrate for endoplasmic-reticulum-associated degradation in C. elegans. PLoS ONE, 7 (7).

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Abstract

Endoplasmic-reticulum associated degradation (ERAD) is a major cellular misfolded protein disposal pathway that is well conserved from yeast to mammals. In yeast, a mutant of carboxypeptidase Y (CPY*) was found to be a luminal ER substrate and has served as a useful marker to help identify modifiers of the ERAD pathway. Due to its ease of genetic manipulation and the ability to conduct a genome wide screen for modifiers of molecular pathways, C. elegans has become one of the preferred metazoans for studying cell biological processes, such as ERAD. However, a marker of ERAD activity comparable to CPY* has not been developed for this model system. We describe a mutant of pro-cathepsin L fused to YFP that no longer targets to the lysosome, but is efficiently eliminated by the ERAD pathway. Using this mutant pro-cathepsin L, we found that components of the mammalian ERAD system that participate in the degradation of ER luminal substrates were conserved in C. elegans. This transgenic line will facilitate high-throughput genetic or pharmacological screens for ERAD modifiers using widefield epifluorescence microscopy. © 2012 Miedel et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Miedel, MT
Graf, NJ
Stephen, KE
Long, OS
Pak, SCscp10@pitt.eduSCP10
Perlmutter, DHdhp6@pitt.eduDHP6
Silverman, GAgas12@pitt.eduGAS12
Luke, CJcjl16@pitt.eduCJL16
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorLamitina, ToddUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 2 July 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 7
DOI or Unique Handle: 10.1371/journal.pone.0040145
Schools and Programs: School of Medicine > Cell Biology and Molecular Physiology
Refereed: Yes
Date Deposited: 11 Jul 2012 18:14
Last Modified: 26 Jan 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/12687

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