Skip Navigation


Human Molecular Genetics Advance Access originally published online on April 6, 2006
Human Molecular Genetics 2006 15(10):1680-1689; doi:10.1093/hmg/ddl091
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
15/10/1680    most recent
ddl091v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Shu, X.
Right arrow Articles by Wright, A. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shu, X.
Right arrow Articles by Wright, A. F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Disease mechanisms in late-onset retinal macular degeneration associated with mutation in C1QTNF5

Xinhua Shu*, Brian Tulloch, Alan Lennon, Dafni Vlachantoni, Xinzhi Zhou, Caroline Hayward and Alan F. Wright

MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK

* To whom correspondence should be addressed. Tel: +44 1313322471; Fax: +44 1314678456; Email: xinhua.shu{at}hgu.mrc.ac.uk

Received January 31, 2006; Accepted March 29, 2006

Late-onset retinal macular degeneration (L-ORMD) is an autosomal dominant condition resembling age-related macular degeneration (AMD) in which a key pathological feature is a thick extracellular sub-retinal pigment epithelial (RPE) deposit. L-ORMD is caused by mutation in the C1QTNF5 (CTRP5) short-chain collagen gene, but the disease mechanism is unknown. Here, we first show that wild-type C1QTNF5 is secreted, whereas mutant C1QTNF5 is misfolded and retained within the endoplasmic reticulum (ER). Secondly, the ER retained mutant protein has a shorter half-life than wild-type C1QTNF5 and is preferentially degraded by proteasomes. Thirdly, C1QTNF5 is shown to interact with the membrane-type frizzled related protein (MFRP), on the basis of yeast two-hybrid, protein pull-down and co-immunoprecipitation assays and RPE co-localization. These data suggest that L-ORMD is due to insufficient levels of secreted C1QTNF5, compromised RPE cell function resulting from ER retention of the mutant protein or both mechanisms.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 FASEB J.Home page
J. H. Jeon, K.-y. Kim, J. H. Kim, A. Baek, H. Cho, Y. H. Lee, J. W. Kim, D. Kim, S. H. Han, J.-S. Lim, et al.
A novel adipokine CTRP1 stimulates aldosterone production
FASEB J, May 1, 2008; 22(5): 1502 - 1511.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
J. Tuo, C. M. Bojanowski, M. Zhou, D. Shen, R. J. Ross, K. I. Rosenberg, D. J. Cameron, C. Yin, J. A. Kowalak, Z. Zhuang, et al.
Murine Ccl2/Cx3cr1 Deficiency Results in Retinal Lesions Mimicking Human Age-Related Macular Degeneration
Invest. Ophthalmol. Vis. Sci., August 1, 2007; 48(8): 3827 - 3836.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
M. N. A. Mandal, V. Vasireddy, M. M. Jablonski, X. Wang, J. R. Heckenlively, B. A. Hughes, G. B. Reddy, and R. Ayyagari
Spatial and Temporal Expression of MFRP and Its Interaction with CTRP5
Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5514 - 5521.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.