title: TRAM regulates the exposure of nascent secretory proteins to the cytosol during translocation into the endoplasmic reticulum.
abstract: Translocational pausing is a mechanism used by certain specialized secretory proteins whereby discrete domains of a nascent chain destined for the endoplasmic reticulum lumen are transiently exposed to the cytosol. Proteoliposomes reconstituted from total endoplasmic reticulum proteins properly assemble translocationally paused intermediates. The capacity of the translocon to correctly pause the nascent chain is dependent on a glycoprotein fraction whose active component is TRAM. In the absence of TRAM, the normally sealed ribosome-membrane junction still opens in response to a pause transfer sequence. However, nascent chain domains that are not exposed to the cytosol in the presence of TRAM are so exposed in its absence. Thus, TRAM regulates which domains of the nascent chain are visible to the cytosol during a translocational pause.
authors.affiliation: Department of Physiology, University of California, San Francisco 94143, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Hegde
authors.forename: S
authors.initials: S
authors.lastname: Voigt
authors.forename: T A
authors.initials: TA
authors.lastname: Rapoport
authors.forename: V R
authors.initials: VR
authors.lastname: Lingappa
mesh_terms: D000818:Animals; D001389:Azirines; D001565:Benzoates; D001692:Biological Transport; D002417:Cattle; D002474:Cell-Free System; D003432:Cross-Linking Reagents; D003600:Cytosol / Q000378:metabolism*; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018871:Endoplasmic Reticulum, Smooth; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D008861:Microsomes / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D018000:Receptors, Peptide / Q000502:physiology; D000069816:SEC Translocation Channels
chemical_list: D001389:Azirines; D001565:Benzoates; D003432:Cross-Linking Reagents; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011498:Protein Precursors; D011510:Proteolipids; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D000069816:SEC Translocation Channels; C020485:proteoliposomes; C036318:signal peptide receptor; C074282:translocating chain-associating membrane protein (TRAM); C017671:preprolactin; C051320:4-(3-trifluoromethyldiazirino)benzoic acid; D011388:Prolactin