The Protein Journal

, Volume 38, Issue 3, pp 289–305 | Cite as

The Ways of Tails: the GET Pathway and more

  • Nica BorgeseEmail author
  • Javier Coy-Vergara
  • Sara Francesca Colombo
  • Blanche SchwappachEmail author


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.


Tail-anchored protein Membrane targeting Endoplasmic reticulum Mitochondrial outer membrane Peroxisomes TRC40 



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.

Supplementary material

10930_2019_9845_MOESM1_ESM.xlsx (47 kb)
Supplementary material 1 (XLS 47 kb)


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of Neuroscience and BIOMETRA DepartmentConsiglio Nazionale delle Ricerche and Università degli Studi di MilanoMilanItaly
  2. 2.Department of Molecular BiologyUniversity of Göttingen Medical CentreGöttingenGermany

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