The GPI (glycosylphosphatidylinositol) moiety is attached to newly synthesized proteins in the lumen of the ER (endoplasmic reticulum). The modified proteins are then directed to the PM (plasma membrane). Less well understood is how nascent mammalian GPI-anchored proteins are targeted from the ER to the PM. In the present study, we investigated mechanisms underlying membrane trafficking of the GPI-anchored proteins, focusing on the early secretory pathway. We first established a cell line that stably expresses inducible temperature-sensitive GPI-fused proteins as a reporter and examined roles of transport-vesicle constituents called p24 proteins in the traffic of the GPI-anchored proteins. We selectively suppressed one of the p24 proteins, namely p23, employing RNAi (RNA interference) techniques. The suppression resulted in pronounced delays of PM expression of the GPI-fused reporter proteins. Furthermore, maturation of DAF (decay-accelerating factor), one of the GPI-anchored proteins in mammals, was slowed by the suppression of p23, indicating delayed trafficking of DAF from the ER to the Golgi. Trafficking of non-GPI-linked cargo proteins was barely affected by p23 knockdown. This is the first to demonstrate direct evidence for the transport of mammalian GPI-anchored proteins being mediated by p24 proteins.
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Research Article|
December 21 2007
Mammalian GPI-anchored proteins require p24 proteins for their efficient transport from the ER to the plasma membrane
Satoshi Takida;
Satoshi Takida
1Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan, and Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan
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Yusuke Maeda;
Yusuke Maeda
1Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan, and Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan
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Taroh Kinoshita
Taroh Kinoshita
1
1Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan, and Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan
1To whom correspondence should be addressed (email tkinoshi@biken.osaka-u.ac.jp).
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Publisher: Portland Press Ltd
Received:
February 13 2007
Revision Received:
September 28 2007
Accepted:
October 11 2007
Accepted Manuscript online:
October 11 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 409 (2): 555–562.
Article history
Received:
February 13 2007
Revision Received:
September 28 2007
Accepted:
October 11 2007
Accepted Manuscript online:
October 11 2007
Citation
Satoshi Takida, Yusuke Maeda, Taroh Kinoshita; Mammalian GPI-anchored proteins require p24 proteins for their efficient transport from the ER to the plasma membrane. Biochem J 15 January 2008; 409 (2): 555–562. doi: https://doi.org/10.1042/BJ20070234
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