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The Ways of Tails: the GET Pathway and more

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Abstract

Due to their topology tail-anchored (TA) proteins must target to the membrane independently of the co-translational route defined by the signal sequence recognition particle (SRP), its receptor and the translocon Sec61. More than a decade of work has extensively characterized a highly conserved pathway, the yeast GET or mammalian TRC40 pathway, which is capable of countering the biogenetic challenge posed by the C-terminal TA anchor. In this review we briefly summarize current models of this targeting route and focus on emerging aspects such as the intricate interplay with the proteostatic network of cells and with other targeting pathways. Importantly, we consider the lessons provided by the in vivo analysis of the pathway in different model organisms and by the consideration of its full client spectrum in more recent studies. This analysis of the state of the field highlights directions in which the current models may be experimentally probed and conceptually extended.

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Acknowledgements

This study was partially supported by a grant of the People Programme (Marie Curie Actions) of the European Union’s Seventh framework Programme FP7/2007-2013/under REA grant agreement n° [607072] to N. Borgese and B. Schwappach. J. Coy-Vergara and B. Schwappach were supported by the Deutsche Forschungsgemeinschaft SFB1002, TP A07 and SFB1190 (P04). We thank A. Farkas for discussion.

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  1. Institute of Neuroscience and BIOMETRA Department, Consiglio Nazionale delle Ricerche and Università degli Studi di Milano, via Vanvitelli 32, 20129, Milan, Italy

    Nica Borgese & Sara Francesca Colombo

  2. Department of Molecular Biology, University of Göttingen Medical Centre, Humboldtallee 23, 37073, Göttingen, Germany

    Javier Coy-Vergara & Blanche Schwappach

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  1. Nica Borgese
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  2. Javier Coy-Vergara
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  3. Sara Francesca Colombo
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Borgese, N., Coy-Vergara, J., Colombo, S.F. et al. The Ways of Tails: the GET Pathway and more. Protein J 38, 289–305 (2019). https://doi.org/10.1007/s10930-019-09845-4

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