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Stress-associated endoplasmic reticulum protein 1 (SERP1)/Ribosome-associated membrane protein 4 (RAMP4) stabilizes membrane proteins during stress and facilitates subsequent glycosylation.

Yamaguchi A, Hori O, Stern DM, Hartmann E, Ogawa S, Tohyama M - J. Cell Biol. (1999)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita City, Osaka 565-0871, Japan.

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.

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Amino acid sequence of rat and human SERP1. The putative transmembrane domain is underlined and the sequence used for raising antibodies is indicated by the box.
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Figure 1: Amino acid sequence of rat and human SERP1. The putative transmembrane domain is underlined and the sequence used for raising antibodies is indicated by the box.

Mentions: Cultured rat astrocytes were exposed to H, and after RT-PCR, a differentially expressed amplicon of 400 bp termed T41 was identified. Northern analysis using this cDNA as a probe and total RNA harvested from hypoxic astrocytes confirmed selective upregulation compared with normoxia (see below), and led us to clone the full-length cDNA. A rat brain cDNA library was screened, and a 2.3-kb cDNA clone was obtained that contained only a single ORF and polyadenylation signal. The cDNA encoded a protein of 66 amino acids, termed SERP1, including a putative transmembrane-spanning domain at the COOH terminus (Fig. 1). Based on sequence homology database searches, SERP1 displayed 29% identity at the amino acid level with the yeast protein YSY6p, which was identified as a high-copy suppressor of SecY/Sec61 mutant (Sakaguchi et al. 1991). Human and Caenorhabditis elegans homologues of SERP1 were encoded in EST clones, and showed 100 and 53% identities, respectively. We further found that SERP1 is identical to a ribosome-associated membrane protein termed RAMP4 which was copurified with Sec61 complex (Görlich and Rapoport 1993). Rat, human, and C. elegans SERP1 cDNA sequences can be obtained from EMBL/GenBank/DDBJ under accession nos. AB018546, AB022427, and Z81095, respectively.


Stress-associated endoplasmic reticulum protein 1 (SERP1)/Ribosome-associated membrane protein 4 (RAMP4) stabilizes membrane proteins during stress and facilitates subsequent glycosylation.

Yamaguchi A, Hori O, Stern DM, Hartmann E, Ogawa S, Tohyama M - J. Cell Biol. (1999)

Amino acid sequence of rat and human SERP1. The putative transmembrane domain is underlined and the sequence used for raising antibodies is indicated by the box.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2168098&req=5

Figure 1: Amino acid sequence of rat and human SERP1. The putative transmembrane domain is underlined and the sequence used for raising antibodies is indicated by the box.
Mentions: Cultured rat astrocytes were exposed to H, and after RT-PCR, a differentially expressed amplicon of 400 bp termed T41 was identified. Northern analysis using this cDNA as a probe and total RNA harvested from hypoxic astrocytes confirmed selective upregulation compared with normoxia (see below), and led us to clone the full-length cDNA. A rat brain cDNA library was screened, and a 2.3-kb cDNA clone was obtained that contained only a single ORF and polyadenylation signal. The cDNA encoded a protein of 66 amino acids, termed SERP1, including a putative transmembrane-spanning domain at the COOH terminus (Fig. 1). Based on sequence homology database searches, SERP1 displayed 29% identity at the amino acid level with the yeast protein YSY6p, which was identified as a high-copy suppressor of SecY/Sec61 mutant (Sakaguchi et al. 1991). Human and Caenorhabditis elegans homologues of SERP1 were encoded in EST clones, and showed 100 and 53% identities, respectively. We further found that SERP1 is identical to a ribosome-associated membrane protein termed RAMP4 which was copurified with Sec61 complex (Görlich and Rapoport 1993). Rat, human, and C. elegans SERP1 cDNA sequences can be obtained from EMBL/GenBank/DDBJ under accession nos. AB018546, AB022427, and Z81095, respectively.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita City, Osaka 565-0871, Japan.

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.

Show MeSH
Related in: MedlinePlus