Motley, A., Hettema, E., Distel, B. et al. (1 more author) (1994) Differential protein import deficiencies in human peroxisome assembly disorders. Journal of Cell Biology, 125 (4). pp. 755-767. ISSN 0021-9525
Abstract
Two peroxisome targeting signals (PTSs) for matrix proteins have been well defined to date. PTS1 comprises a COOH-terminal tripeptide, SKL, and has been found in several matrix proteins, whereas PTS2 has been found only in peroxisomal thiolase and is contained within an NH2-terminal cleavable presequence. We have investigated the functional integrity of the import routes for PTS1 and PTS2 in fibroblasts from patients suffering from peroxisome assembly disorders. Three of the five complementation groups tested showed a general loss of PTS1 and PTS2 import. Two complementation groups showed a differential loss of peroxisomal protein import: group I cells were able to import a PTS1- but not a PTS2- containing reporter protein into their peroxisomes, and group IV cells were able to import the PTS2 but not the PTS1 reporter into aberrant, peroxisomal ghostlike structures. The observation that the PTS2 import pathway is intact only in group IV cells is supported by the protection of endogenous thiolase from protease degradation in group IV cells and its sensitivity in the remaining complementation groups, including the partialized disorder of group I. The functionality of the PTS2 import pathway and colocalization of endogenous thiolase with the peroxisomal membranes in group IV cells was substantiated further using immunofluorescence, subcellular fractionation, and immunoelectron microscopy. The phenotypes of group I and IV cells provide the first evidence for differential import deficiencies in higher eukaryotes. These phenotypes are analogous to those found in Saccharomyces cerevisiae peroxisome assembly mutants.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 1994 Rockefeller University Press. CC BY-NC-SA |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 Dec 2016 14:57 |
Last Modified: | 05 Dec 2016 14:57 |
Published Version: | http://dx.doi.org/10.1083/jcb.125.4.755 |
Status: | Published |
Publisher: | Rockefeller University Press |
Refereed: | Yes |
Identification Number: | 10.1083/jcb.125.4.755 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:108667 |