Mice lacking WRB reveal differential biogenesis requirements of tail-anchored 
proteins in vivo.

Rivera-Monroy, J.; Musiol, L.; Unthan-Fechner, K.; Farkas, A.; Clancy, A.; Coy-Vergara, J.; Weill, U.; Gockel, S.; Lin, S. Y.; Corey, D. P.; Kohl, T.; Strobel, P.; Schuldiner, M.; Schwappach, B.; Vilardi, F.

doi:10.1038/srep39464

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Mice lacking WRB reveal differential biogenesis requirements of tail-anchored proteins in vivo.

MPS-Authors

There are no MPG-Authors in the publication available

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

2381746.pdf
(Publisher version), 3MB

Supplementary Material (public)

2381746_Suppl_1.pdf
(Supplementary material), 4MB

2381746_Suppl_2.zip
(Supplementary material), 70KB

Citation

Rivera-Monroy, J., Musiol, L., Unthan-Fechner, K., Farkas, A., Clancy, A., Coy-Vergara, J., et al. (2016). Mice lacking WRB reveal differential biogenesis requirements of tail-anchored proteins in vivo. Scientific Reports, 6: 39464. doi:10.1038/srep39464.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002C-3925-D

Abstract

Tail-anchored (TA) proteins are post-translationally inserted into membranes. The TRC40 pathway targets TA proteins to the endoplasmic reticulum via a receptor comprised of WRB and CAML. TRC40 pathway clients have been identified using in vitro assays, however, the relevance of the TRC40 pathway in vivo remains unknown. We followed the fate of TA proteins in two tissue-specific WRB knockout mouse models and found that their dependence on the TRC40 pathway in vitro did not predict their reaction to receptor depletion in vivo. The SNARE syntaxin 5 (Stx5) was extremely sensitive to disruption of the TRC40 pathway. Screening yeast TA proteins with mammalian homologues, we show that the particular sensitivity of Stx5 is conserved, possibly due to aggregation propensity of its cytoplasmic domain. We establish that Stx5 is an autophagy target that is inefficiently membrane-targeted by alternative pathways. Our results highlight an intimate relationship between the TRC40 pathway and cellular proteostasis.