Publication details for Prof Roy Andrew QuinlanElliott, J.L., Der Perng, M., Prescott, A.R., Jansen, K.A., Koenderink, G.H. & Quinlan, R.A. (2013). The specificity of the interaction between αB-crystallin and desmin filaments and its impact on filament aggregation and cell viability. Philosophical Transactions of the Royal Society B: Biological Sciences 368(1617): 20120375.
- Publication type: Journal Article
- ISSN/ISBN: 0962-8436 (print), 1471-2970 (electronic)
- DOI: 10.1098/rstb.2012.0375
- Keywords: αB-crystallin/CRYAB/HSPB5, Desmin-related myopathy, Desmin intermediate filament, Crystallinopathy, Cardiomyopathy.
- Further publication details on publisher web site
- Durham Research Online (DRO) - may include full text
Author(s) from Durham
CRYAB (αB-crystallin) is expressed in many tissues and yet the R120G mutation in CRYAB causes tissue-specific pathologies, namely cardiomyopathy and cataract. Here, we present evidence to demonstrate that there is a specific functional interaction of CRYAB with desmin intermediate filaments that predisposes myocytes to disease caused by the R120G mutation. We use a variety of biochemical and biophysical techniques to show that plant, animal and ascidian small heat-shock proteins (sHSPs) can interact with intermediate filaments. Nevertheless, the mutation R120G in CRYAB does specifically change that interaction when compared with equivalent substitutions in HSP27 (R140G) and into the Caenorhabditis elegans HSP16.2 (R95G). By transient transfection, we show that R120G CRYAB specifically promotes intermediate filament aggregation in MCF7 cells. The transient transfection of R120G CRYAB alone has no significant effect upon cell viability, although bundling of the endogenous intermediate filament network occurs and the mitochondria are concentrated into the perinuclear region. The combination of R120G CRYAB co-transfected with wild-type desmin, however, causes a significant reduction in cell viability. Therefore, we suggest that while there is an innate ability of sHSPs to interact with and to bind to intermediate filaments, it is the specific combination of desmin and CRYAB that compromises cell viability and this is potentially the key to the muscle pathology caused by the R120G CRYAB.