Cookies

We use cookies to ensure that we give you the best experience on our website. By continuing to browse this repository, you give consent for essential cookies to be used. You can read more about our Privacy and Cookie Policy.


Durham Research Online
You are in:

Desmin aggregate formation by R120G alpha B-crystallin is caused byaltered filament interactions and is dependent upon network status in cells.

Perng, M. D. and Wen, S. F. and van den Ijssel, P. and Prescott, A. R. and Quinlan, R. A. (2004) 'Desmin aggregate formation by R120G alpha B-crystallin is caused byaltered filament interactions and is dependent upon network status in cells.', Molecular biology of the cell., 15 (5). pp. 2335-2346.

Abstract

The R120G mutation in alphaB-crystallin causes desmin-related myopathy. There have been a number of mechanisms proposed to explain the disease process, from altered protein processing to loss of chaperone function. Here, we show that the mutation alters the in vitro binding characteristics of alphaB-crystallin for desmin filaments. The apparent dissociation constant of R120G alphaB-crystallin was decreased while the binding capacity was increased significantly and as a result, desmin filaments aggregated. These data suggest that the characteristic desmin aggregates seen as part of the disease histopathology can be caused by a direct, but altered interaction of R120G alphaB-crystallin with desmin filaments. Transfection studies show that desmin networks in different cell backgrounds are not equally affected. Desmin networks are most vulnerable when they are being made de novo and not when they are already established. Our data also clearly demonstrate the beneficial role of wild-type alphaB-crystallin in the formation of desmin filament networks. Collectively, our data suggest that R120G alphaB-crystallin directly promotes desmin filament aggregation, although this gain of a function can be repressed by some cell situations. Such circumstances in muscle could explain the late onset characteristic of the myopathies caused by mutations in alphaB-crystallin.

Item Type:Article
Full text:PDF - Published Version (749Kb)
Status:Peer-reviewed
Publisher Web site:http://dx.doi.org/10.1091/mbc.E03-12-0893
Publisher statement:© 2004 by The American Society for Cell Biology
Record Created:01 Oct 2008
Last Modified:26 Aug 2011 14:22

Social bookmarking: del.icio.usConnoteaBibSonomyCiteULikeFacebookTwitterExport: EndNote, Zotero | BibTex
Usage statisticsLook up in GoogleScholar | Find in a UK Library