Signal recognition particle mediates post-translational targeting in eukaryotes.
Signal recognition particle (SRP) plays a central role in the delivery of classical secretory and membrane proteins to the endoplasmic reticulum (ER). All nascent chains studied to date dissociate from SRP once released from the ribosome, thereby supporting a strictly cotranslational mode of action for eukaryotic SRP. We now report a novel post-translational function for SRP in the targeting of tail-anchored (TA) proteins to the ER. TA proteins possess a hydrophobic membrane insertion sequence at their C-terminus such that it can only emerge from the ribosome after translation is terminated. We show that SRP can associate post-translationally with this type of ER-targeting signal, and deliver newly synthesised TA proteins to the ER membrane by a pathway dependent upon GTP and the SRP receptor. We find that dependency upon this SRP-dependent route is precursor specific, and propose a unifying model to describe the biogenesis of TA proteins in vivo.
Abell
Benjamin M
BM
School of Biological Sciences, University of Manchester, Manchester, UK.
Pool
Martin R
MR
Schlenker
Oliver
O
Sinning
Irmgard
I
High
Stephen
S
D000595:Amino Acid Sequence; D000818:Animals; D002474:Cell-Free System; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005057:Eukaryotic Cells / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D008969:Molecular Sequence Data; D011485:Protein Binding; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D018271:Signal Recognition Particle / Q000378:metabolism*
D008565:Membrane Proteins; D021382:Protein Sorting Signals; D018271:Signal Recognition Particle; D006160:Guanosine Triphosphate