Stress-associated endoplasmic reticulum protein 1 (SERP1)/Ribosome-associated membrane protein 4 (RAMP4) stabilizes membrane proteins during stress and facilitates subsequent glycosylation.
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.
Mesh Terms:
Amino Acid Sequence, Animals, Astrocytes, Brain Ischemia, Calcium-Binding Proteins, Calnexin, Cell Hypoxia, Cell Line, Cloning, Molecular, Endoplasmic Reticulum, Glycoproteins, Glycosylation, Homeostasis, Humans, Male, Membrane Proteins, Molecular Chaperones, Molecular Sequence Data, Protein Binding, Protein Denaturation, Protein Renaturation, RNA, Messenger, Rats, Rats, Sprague-Dawley, Sequence Homology, Amino Acid
Amino Acid Sequence, Animals, Astrocytes, Brain Ischemia, Calcium-Binding Proteins, Calnexin, Cell Hypoxia, Cell Line, Cloning, Molecular, Endoplasmic Reticulum, Glycoproteins, Glycosylation, Homeostasis, Humans, Male, Membrane Proteins, Molecular Chaperones, Molecular Sequence Data, Protein Binding, Protein Denaturation, Protein Renaturation, RNA, Messenger, Rats, Rats, Sprague-Dawley, Sequence Homology, Amino Acid
J. Cell Biol.
Date: Dec. 13, 1999
PubMed ID: 10601334
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