Signal recognition particle-dependent targeting of ribosomes to the rough endoplasmic reticulum in the absence and presence of the nascent polypeptide-associated complex.
Proteins with RER-specific signal sequences are cotranslationally translocated across the rough endoplasmic reticulum through a proteinaceous channel composed of oligomers of the Sec61 complex. The Sec61 complex also binds ribosomes with high affinity. The dual function of the Sec61 complex necessitates a mechanism to prevent signal sequence-independent binding of ribosomes to the translocation channel. We have examined the hypothesis that the signal recognition particle (SRP) and the nascent polypeptide-associated complex (NAC), respectively, act as positive and negative regulatory factors to mediate the signal sequence-specific attachment of the ribosome-nascent chain complex (RNC) to the translocation channel. Here, SRP-independent translocation of a nascent secretory polypeptide was shown to occur in the presence of endogenous wheat germ or rabbit reticulocyte NAC. Furthermore, SRP markedly enhanced RNC binding to the translocation channel irrespective of the presence of NAC. Binding of RNCs, but not SRP-RNCs, to the Sec61 complex is competitively inhibited by 80S ribosomes. Thus, the SRP-dependent targeting pathway provides a mechanism for delivery of RNCs to the translocation channel that is not inhibited by the nonselective interaction between the ribosome and the Sec61 complex.
Raden
D
D
Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01655-0103, USA.
Gilmore
R
R
D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D004285:Dogs; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism*; D018832:Molecular Chaperones; D010179:Pancreas / Q000166:cytology; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000378:metabolism; D011506:Proteins / Q000502:physiology*; D011817:Rabbits; D012270:Ribosomes / Q000378:metabolism*; D012639:Seeds / Q000378:metabolism; D018271:Signal Recognition Particle / Q000037:antagonists & inhibitors / Q000502:physiology*; D015534:Trans-Activators; D014908:Triticum / Q000378:metabolism
D018832:Molecular Chaperones; D021382:Protein Sorting Signals; D011506:Proteins; D018271:Signal Recognition Particle; D015534:Trans-Activators; C096099:nascent-polypeptide-associated complex