Bishop, P., Rubin, P., Thomson, A. R. , Rocca, D. and Henley, J. M. (2014) The ubiquitin C-terminal hydrolase L1 (UCH-L1) C terminus plays a key role in protein stability, but its farnesylation is not required for membrane association in primary neurons. Journal of Biological Chemistry, 289(52), pp. 36140-36149. (doi: 10.1074/jbc.M114.557124) (PMID:25326379) (PMCID:PMC4276877)
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Abstract
Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is highly expressed in neurons. A possible role for UCH-L1 in neurodegeneration has been highlighted because of its presence in Lewy bodies associated with Parkinson disease and neurofibrillary tangles observed in Alzheimer disease. UCH-L1 exists in two forms in neurons, a soluble cytoplasmic form (UCH-L1C) and a membrane-associated form (UCH-L1M). Alzheimer brains show reduced levels of soluble UCH-L1C correlating with the formation of UCH-L1-immunoreactive tau tangles, whereas UCH-L1M has been implicated in α-synuclein dysfunction. Given these reports of divergent roles, we investigated the properties of UCH-L1 membrane association. Surprisingly, our results indicate that UCH-L1 does not partition to the membrane in the cultured cell lines we tested. Furthermore, in primary cultured neurons, a proportion of UCH-L1M does partition to the membrane, but, contrary to a previous report, this does not require farnesylation. Deletion of the four C-terminal residues caused the loss of protein solubility, abrogation of substrate binding, increased cell death, and an abnormal intracellular distribution, consistent with protein dysfunction and aggregation. These data indicate that UCH-L1 is differently processed in neurons compared with clonal cell lines and that farnesylation does not account for the membrane association in neurons.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Thomson, Dr Drew |
Authors: | Bishop, P., Rubin, P., Thomson, A. R., Rocca, D., and Henley, J. M. |
College/School: | College of Science and Engineering > School of Chemistry |
Journal Name: | Journal of Biological Chemistry |
Publisher: | American Society for Biochemistry and Molecular Biology, Inc. |
ISSN: | 0021-9258 |
ISSN (Online): | 1083-351X |
Published Online: | 17 October 2014 |
Copyright Holders: | Copyright © 2014 The American Society for Biochemistry and Molecular Biology, Inc. |
First Published: | First published in Journal of Biological Chemistry 289(52): 36140-36149 |
Publisher Policy: | Reproduced under a Creative Commons License |
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