Emery-Dreifuss muscular dystrophy mutations impair TRC40-mediated targeting of emerin to the inner nuclear membrane
2016 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Emery-Dreifuss muscular dystrophy mutations impair TRC40-mediated targeting of emerin to the inner nuclear membrane
Pfaff, J. ; Monroy, J. R.; Jamieson, C.; Rajanala, K.; Vilardi, F.; Schwappach, B. & Kehlenbach, R. H. (2016)
Journal of Cell Science, 129(3) pp. 502-516. DOI: https://doi.org/10.1242/jcs.179333
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Details
- Authors
- Pfaff, Janine ; Monroy, Jhon Rivera; Jamieson, Cara; Rajanala, Kalpana; Vilardi, Fabio; Schwappach, Blanche ; Kehlenbach, Ralph H.
- Abstract
- Emerin is a tail-anchored protein that is found predominantly at the inner nuclear membrane (INM), where it associates with components of the nuclear lamina. Mutations in the emerin gene cause Emery-Dreifuss muscular dystrophy (EDMD), an X-linked recessive disease. Here, we report that the TRC40/GET pathway for post-translational insertion of tail-anchored proteins into membranes is involved in emerin-trafficking. Using proximity ligation assays, we show that emerin interacts with TRC40 in situ. Emerin expressed in bacteria or in a cell-free lysate was inserted into microsomal membranes in an ATP- and TRC40-dependent manner. Dominant-negative fragments of the TRC40-receptor proteins WRB and CAML (also known as CAMLG) inhibited membrane insertion. A rapamycin-based dimerization assay revealed correct transport of wild-type emerin to the INM, whereas TRC40-binding, membrane integration and INM-targeting of emerin mutant proteins that occur in EDMD was disturbed. Our results suggest that the mode of membrane integration contributes to correct targeting of emerin to the INM.
- Issue Date
- 2016
- Journal
- Journal of Cell Science
- Project
- SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz
SFB 1002 | A07: Rolle der TRC40-Maschinerie im Proteostase-Netzwerk von Kardiomyozyten - Working Group
- RG Schwappach (Membrane Protein Biogenesis)
- ISSN
- 0021-9533; 1477-9137
- Language
- English