title: Cotranslational Intersection between the SRP and GET Targeting Pathways to the Endoplasmic Reticulum of Saccharomyces cerevisiae.
abstract: 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.
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, Freiburg, Germany.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, Freiburg, Germany.
authors.forename: Thea
authors.initials: T
authors.lastname: Schäffer
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, Freiburg, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Wölfle
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, Freiburg, Germany.
authors.forename: Edith
authors.initials: E
authors.lastname: Fitzke
authors.affiliation: Institute of Botany, Technische Universität Darmstadt, Darmstadt, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Thiel
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, Freiburg, Germany Center for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany sabine.rospert@biochemie.uni-freiburg.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Rospert
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D014176:Protein Biosynthesis; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D018271:Signal Recognition Particle / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D015221:Potassium Channels; D029701:Saccharomyces cerevisiae Proteins; D018271:Signal Recognition Particle