Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: APOPTOSIS ; CELLS ; IN-VITRO ; Germany ; human ; IN-VIVO ; DISEASE ; GENE ; GENES ; PROTEIN ; DOMAIN ; CLEAVAGE ; resistance ; MUTATIONS ; intermediate filaments ; INTERMEDIATE-FILAMENTS ; vimentin ; ALPHA-B-CRYSTALLIN ; EPIDERMOLYSIS-BULLOSA SIMPLEX ; MICE LACKING VIMENTIN ; CYTOTOXICITY ; assembly ; keratins ; aggregates
    Abstract: To get new insights into the function of the intermediate filament (IF) protein vimentin in cell physiology, we generated two mutant cDNAs, one with a point mutation in the consensus motif in coillA (R113C) and one with the complete deletion of coil 2B of the rod domain. In keratins and glia filament protein (GFAP). analogous mutations cause keratinopathies and Alexander disease, respectively. Both mutants prevented filament assembly in vitro and inhibited assembly of wild-type vimentin when present in equal amounts. In stably transfected preadipocytes, these mutants caused the complete disruption of the endogenous vimentin network, demonstrating their dominant-negative behaviour. Cytoplasmic vimentin aggregates colocalised with the chaperones alpha B-crystallin and HSP40. Moreover, vimR(113)C mutant cells were more resistant against staurosporine-induced apoptosis compared to controls. We hypothesise that mutations in the vimentin gene, like in most classes of IF genes, may contribute to distinct human diseases. (c) 2005 Elsevier GmbH. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 16373170
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: ADULT, aggregates, AGGREGATION, ALEXANDER-DISEASE, ALLELE, analysis, BIOLOGY, CELL, CELLS, CHRONIC H
    Abstract: Mutations in genes encoding epidermal keratins cause skin disorders, while those in internal epithelial keratins, such as K8 and K18, are risk factors for liver diseases. The effect of dominant mutations in K8 or K18 during embryonic development and tissue homeostasis has not been examined so far. Here we demonstrate that the dominant mutation hK18 R89C, that is highly similar to hK14 R125C, causing EBS in humans, leads to cell type-specific lethality in mice, depending on the ratio of mutant to endogenous keratins. Mice expressing hK18 R89C in the absence of endogenous K19 and K18 died at mid-gestation from defects in trophoblast giant cells, accompanied by haematomas. A single, endogenous K18 allele rescued embryonic lethality but caused aggregation of keratins in all adult internal epithelia, surprisingly without spontaneous cell fragility. Closer analysis revealed that both filaments and aggregates coexisted in the same cell, depending on the ratio of mutant to endogenous keratins. Our results demonstrate that balanced overexpression of a wild-type keratin rescued the lethal consequences of a dominant-negative mutation. This has important implications for therapy approaches of keratinopathies, suggesting that suppressing the mutant allele is not necessary in vivo. (c) 2007 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 17617404
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...