Rab GTPase prenylation hierachy and its potential role in Choroideremia disease

Kohnke, Monika, Delon, Christine, Hastie, Marcus L., Nguyen, Uyen T. T., Wu, Yao-Wen, Waldmann, Herbert, Goody, Roger S., Gorman, Jeffrey J. and Alexandrov, Kirill (2013) Rab GTPase prenylation hierachy and its potential role in Choroideremia disease. PloS One, 8 2: . doi:10.1371/journal.pone.0081758

Author Kohnke, Monika
Delon, Christine
Hastie, Marcus L.
Nguyen, Uyen T. T.
Wu, Yao-Wen
Waldmann, Herbert
Goody, Roger S.
Gorman, Jeffrey J.
Alexandrov, Kirill
Title Rab GTPase prenylation hierachy and its potential role in Choroideremia disease
Journal name PloS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-12-01
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0081758
Open Access Status DOI
Volume 8
Issue 2
Total pages 11
Place of publication San Francisco, United States
Publisher Public Library of Science
Language eng
Subject 1300 Biochemistry, Genetics and Molecular Biology
1100 Agricultural and Biological Sciences
Abstract Protein prenylation is a widespread post-translational modification in eukaryotes that plays a crucial role in membrane targeting and signal transduction. RabGTPases is the largest group of post-translationally C-terminally geranylgeranylated. All Rabs are processed by Rab geranylgeranyl-transferase and Rab escort protein (REP). Human genetic defects resulting in the loss one of two REP isoforms REP-1, lead to underprenylation of RabGTPases that manifests in retinal degradation and blindness known as choroideremia. In this study we used a combination of microinjections and chemo-enzymatic tagging to establish whether Rab GTPases are prenylated and delivered to their target cellular membranes with the same rate. We demonstrate that although all tested Rab GTPases display the same rate of membrane delivery, the extent of Rab prenylation in 5 hour time window vary by more than an order of magnitude. We found that Rab27a, Rab27b, Rab38 and Rab42 display the slowest prenylation in vivo and in the cell. Our work points to possible contribution of Rab38 to the emergence of choroideremia in addition to Rab27a and Rab27b.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP1094080
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 12 times in Scopus Article | Citations
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Created: Tue, 17 Dec 2013, 22:29:59 EST by Susan Allen on behalf of Institute for Molecular Bioscience