Cotranslational Intersection between the SRP and GET Targeting Pathways to the Endoplasmic Reticulum of Saccharomyces cerevisiae

Mol Cell Biol. 2016 Aug 26;36(18):2374-83. doi: 10.1128/MCB.00131-16. Print 2016 Sep 15.


Targeting of transmembrane proteins to the endoplasmic reticulum (ER) proceeds via either the signal recognition particle (SRP) or the guided entry of tail-anchored proteins (GET) pathway, consisting of Get1 to -5 and Sgt2. While SRP cotranslationally targets membrane proteins containing one or multiple transmembrane domains, the GET pathway posttranslationally targets proteins containing a single C-terminal transmembrane domain termed the tail anchor. Here, we dissect the roles of the SRP and GET pathways in the sorting of homologous, two-membrane-spanning K(+) channel proteins termed Kcv, Kesv, and Kesv-VV. We show that Kcv is targeted to the ER cotranslationally via its N-terminal transmembrane domain, while Kesv-VV is targeted posttranslationally via its C-terminal transmembrane domain, which recruits Get4-5/Sgt2 and Get3. Unexpectedly, nascent Kcv recruited not only SRP but also the Get4-5 module of the GET pathway to ribosomes. Ribosome binding of Get4-5 was independent of Sgt2 and was strongly outcompeted by SRP. The combined data indicate a previously unrecognized cotranslational interplay between the SRP and GET pathways.

MeSH terms

  • Carrier Proteins / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Potassium Channels / metabolism*
  • Protein Biosynthesis
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Recognition Particle / metabolism*
  • Transcription, Genetic


  • Carrier Proteins
  • Potassium Channels
  • Saccharomyces cerevisiae Proteins
  • Signal Recognition Particle

Grant support

This work was funded by grants from the Deutsche Forschungsgemeinschaft (DFG) to Sabine Rospert (BIOSS-2, SFB 746, and RO 1028/5-1) and to Gerhard Thiel (TH 558/8-2).