Regulation of ribosome detachment from the mammalian endoplasmic reticulum membrane.
In current models, protein translocation in the endoplasmic reticulum (ER) occurs in the context of two cycles, the signal recognition particle (SRP) cycle and the ribosome cycle. Both SRP and ribosomes bind to the ER membrane as a consequence of the targeting process of translocation. Whereas SRP release from the ER membrane is regulated by the GTPase activities of SRP and the SRP receptor, ribosome release from the ER membrane is thought to occur in response to the termination of protein synthesis. We report that ER-bound ribosomes remain membrane-bound following the termination of protein synthesis and in the bound state can initiate the translation of secretory and cytoplasmic proteins. Two principal observations are reported. 1) Membrane-bound ribosomes engaged in the synthesis of proteins lacking a signal sequence are released from the ER membrane as ribosome-nascent polypeptide complexes. 2) Membrane-bound ribosomes translating secretory proteins can access the translocon in an SRP receptor-independent manner. We propose that ribosome release from the ER membrane occurs in the context of protein translation, with release occurring by default in the absence of productive nascent polypeptide-membrane interactions.
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
M D
MD
Potter
C V
CV
Nicchitta
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D014176:Protein Biosynthesis; D011487:Protein Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*
D010455:Peptides; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; C036318:signal peptide receptor