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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., et al. (2016). Emery-Dreifuss muscular dystrophy mutations impair TRC40-mediated targeting of emerin to the inner nuclear membrane. Journal of Cell Science, 129(3), 502-516. doi:10.1242/jcs.179333.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-B901-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-0B0D-6
Genre: Journal Article

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 Creators:
Pfaff, J., Author
Monroy, J. R., Author
Jamieson, C., Author
Rajanala, K., Author
Vilardi, F., Author
Schwappach, B.1, Author              
Kehlenbach, R. H., Author
Affiliations:
1Max Planck Fellow Blanche Schwappach, ou_1548137              

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Free keywords: CAML; TRC40; WRB; Emerin; Inner nuclear membrane; Tail-anchored protein
 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.

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Language(s): eng - English
 Dates: 2015-12-162016-02-01
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1242/jcs.179333
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Title: Journal of Cell Science
Source Genre: Journal
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Pages: - Volume / Issue: 129 (3) Sequence Number: - Start / End Page: 502 - 516 Identifier: -