Journal Article

Dominant cataract formation in association with a vimentin assembly disrupting mutation

Martin Müller, Shomi S. Bhattacharya, Tony Moore, Quincy Prescott, Tatjana Wedig, Harald Herrmann and Thomas M. Magin

in Human Molecular Genetics

Volume 18, issue 6, pages 1052-1057
Published in print March 2009 | ISSN: 0964-6906
Published online January 2009 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddn440
Dominant cataract formation in association with a vimentin assembly disrupting mutation

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Cataracts are characterized by an opacification of the eye lens, often caused by protein misfolding and aggregation. The intermediate filament protein vimentin, which is highly expressed in lens fiber cells and in mesenchymal tissues, is a main structural determinant in these cells forming a membrane-connected cytoskeleton. Additional functions of vimentin remain to be identified. Here, we demonstrate that a mutation in VIM causes a dominant, pulverulent cataract. We sequenced the complete human VIM gene in 90 individuals suffering from congenital cataract and found a G596A change in exon 1 in a single individual, causing the missense mutation E151K in coil 1B of vimentin. The mutant vimentin formed an aberrant vimentin cytoskeleton and increased the proteasome activity in transfected cells. Furthermore, this mutation causes a severe kinetic defect in vimentin assembly both in vitro and in vivo. Hence, in conjunction with available mouse and cell culture models, our results reveal for the first time an important functional role for vimentin in the maintenance of lens integrity. Finally, this invites novel therapy approaches for cataracts.

Journal Article.  2730 words.  Illustrated.

Subjects: Genetics and Genomics

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