The cargo receptor ERGIC-53 is a target of the unfolded protein response.
The accumulation of unfolded proteins in the ER triggers a signaling response known as unfolded protein response (UPR). In yeast the UPR affects several hundred genes that encode ER chaperones and proteins operating at later stages of secretion. In mammalian cells the UPR appears to be more limited to chaperones of the ER and genes assumed to be important after cell recovery from ER stress that are not important for secretion. Here, we report that the mRNA of lectin ERGIC-53, a cargo receptor for the transport of glycoproteins from ER to ERGIC, and of its related protein VIP36 is induced by the known inducers of ER stress, tunicamycin and thapsigargin. In parallel, the rate of synthesis of the ERGIC-53 protein was induced by these agents. The response was due to the UPR since it was also triggered by castanospermine, a specific inducer of UPR, and inhibited by genistein. Thapsigargin-induced upregulation of ERGIC-53 could be fully accounted for by the ATF6 pathway of UPR. The results suggest that in mammalian cells the UPR also affects traffic from and beyond the ER.
Department of Pharmacology and Neurobiology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Beat
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Nyfeler
Oliver
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Nufer
Toshie
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Matsui
Kazutoshi
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Mori
Hans-Peter
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Hauri
D051702:Activating Transcription Factor 6; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008715:Methionine / Q000378:metabolism; D017510:Protein Folding; D012333:RNA, Messenger / Q000378:metabolism; D019284:Thapsigargin / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014415:Tunicamycin / Q000378:metabolism
C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C084004:LMAN1 protein, human; C086797:LMAN2 protein, human; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014415:Tunicamycin; D019284:Thapsigargin; D008715:Methionine