Stress-Associated Endoplasmic Reticulum Protein 1 (Serp1)/Ribosome-Associated Membrane Protein 4 (Ramp4) Stabilizes Membrane Proteins during Stress and Facilitates Subsequent Glycosylation
Open Access
- 13 December 1999
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 147 (6), 1195-1204
- https://doi.org/10.1083/jcb.147.6.1195
Abstract
Application of differential display to cultured rat astrocytes subjected to hypoxia allowed cloning of a novel cDNA, termed stress-associated endoplasmic reticulum protein 1 (SERP1). Expression of SERP1 was enhanced in vitro by hypoxia and/or reoxygenation or other forms of stress, causing accumulation of unfolded proteins in endoplasmic reticulum (ER) stress, and in vivo by middle cerebral artery occlusion in rats. The SERP1 cDNA encodes a 66-amino acid polypeptide which was found to be identical to ribosome-associated membrane protein 4 (RAMP4) and bearing 29% identity to yeast suppressor of SecY 6 protein (YSY6p), suggesting participation in pathways controlling membrane protein biogenesis at ER. In cultured 293 cells subjected to ER stress, overexpression of SERP1/RAMP4 suppressed aggregation and/or degradation of newly synthesized integral membrane proteins, and subsequently, facilitated their glycosylation when the stress was removed. SERP1/RAMP4 interacted with Sec61alpha and Sec61beta, which are subunits of translocon, and a molecular chaperon calnexin. Furthermore, Sec61alpha and Sec61beta, but not SERP1/RAMP4, were found to associate with newly synthesized integral membrane proteins under stress. These results suggest that stabilization of membrane proteins in response to stress involves the concerted action of a rescue unit in the ER membrane comprised of SERP1/RAMP4, other components of translocon, and molecular chaperons in ER.Keywords
This publication has 43 references indexed in Scilit:
- The Mechanism Underlying Cystic Fibrosis Transmembrane Conductance Regulator Transport from the Endoplasmic Reticulum to the Proteasome Includes Sec61β and a Cytosolic, Deglycosylated IntermediaryJournal of Biological Chemistry, 1998
- The β Subunit of the Sec61 Complex Facilitates Cotranslational Protein Transport and Interacts with the Signal Peptidase during TranslocationThe Journal of cell biology, 1998
- 150-kD oxygen-regulated protein is expressed in human atherosclerotic plaques and allows mononuclear phagocytes to withstand cellular stress on exposure to hypoxia and modified low density lipoprotein.JCI Insight, 1996
- Purification and Characterization of a Novel Stress Protein, the 150-kDa Oxygen-regulated Protein (ORP150), from Cultured Rat Astrocytes and Its Expression in Ischemic Mouse BrainPublished by Elsevier ,1996
- Cloning of a Novel RNA Binding Polypeptide (RA301) Induced by Hypoxia/ReoxygenationJournal of Biological Chemistry, 1995
- Cloning of rat grp75, an hsp70‐family member, and its expression in normal and ischemic brainJournal of Neuroscience Research, 1995
- Excitotoxicity and the NMDA receptor -- still lethal after eight yearsTrends in Neurosciences, 1995
- Metabolic and Biosynthetic Alterations in Cultured Astrocytes Exposed to Hypoxia/ReoxygenationJournal of Neurochemistry, 1994
- Protein translocation into proteoliposomes reconstituted from purified components of the endoplasmic reticulum membraneCell, 1993
- Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue.The Journal of cell biology, 1980