Luminal/extracellular domains of chimeric CI-M6PR-C proteins interfere with their retrograde endosome-to-TGN trafficking in the transient expression system

Fei Chang; Na Li; Kang Yan; Yumin Huang; Hongfei Xu; Yongjian Liu

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Luminal/extracellular domains of chimeric CI-M6PR-C proteins interfere with their retrograde endosome-to-TGN trafficking in the transient expression system

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cqvip:The membrane trafficking of cation-independent mannose 6-phosphate receptor(CI-M6PR) between the transGolgi network(TGN) and endosomal compartments is not only critical for maintaining lysosomal function but also a well-known event for understanding molecular and cellular mechanisms in retrograde endosome-to-TGN trafficking.Although it has been well established in literature that the C-terminus of bovine CI-M6PR determines its retrograde trafficking,it remains unclear whether the luminal domain of the protein plays a role on these sorting events.In this study,we found that partial deletion of luminal domain of human CI-M6PR mistargeted the mutant protein to nonTGN compartments.Moreover,replacing the luminal domain of both bovine and human CI-M6PR with that from irrelevant membrane proteins such as CD8 or Tac also altered the TGN targeting of the chimeric proteins.On the other hand,only short sequence from HA fused with the transmembrane domain and C-terminus of the receptor,HA-hCIM6PR-tail,resulted in its preferential targeting to TGN as for the full length receptor,strongly suggesting that sorting of the receptor may be influenced by luminal sequence.Furthermore,using this luminal truncated form of HA-hCIM6 PR as a model cargo,we found that the trafficking of the chimeric protein was regulated by the retromer complex through interacting with SNX5.In conclusion,our study strongly suggested that the disrupted luminal domain from hCI-M6PR or other irrelevant membrane proteins interfere with the process of membrane trafficking and TGN targeting of CI-M6PR.

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《生物医学研究杂志：英文版》 |2018年第4期|P.245-256|共12页
作者
Fei Chang; Na Li; Kang Yan; Yumin Huang; Hongfei Xu; Yongjian Liu;
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作者单位

[1]jiangsu Key Laboratory of Xenotransplanation;

Department of Medical Genetics;

Nanjing Medical University;

Nanjing;

Jiangsu 211166;

China;

[1]jiangsu Key Laboratory of Xenotransplanation;

Department of Medical Genetics;

Nanjing Medical University;

Nanjing;

Jiangsu 211166;

China;

[1]jiangsu Key Laboratory of Xenotransplanation;

Department of Medical Genetics;

Nanjing Medical University;

Nanjing;

Jiangsu 211166;

China;

[2]Department of Orthopedics;

the First Affiliated Hospital of Nanjing Medical University;

Nanjing;

Jiangsu 210029;

China;

[1]jiangsu Key Laboratory of Xenotransplanation;

Department of Medical Genetics;

Nanjing Medical University;

Nanjing;

Jiangsu 211166;

China;

[1]jiangsu Key Laboratory of Xenotransplanation;

Department of Medical Genetics;

Nanjing Medical University;

Nanjing;

Jiangsu 211166;

China;

[3]Department of Pharmacology ＆ Chemical Biology;

University of Pittsburgh School of Medicine;

Pittsburgh;

PA 15213;

USA;

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原文格式 PDF
正文语种 CHI
中图分类 TQ126.35;
关键词
蛋白质; 表达式; 统防; 磷酸盐; 甘露糖; 阳离子; 膜;

机译：蛋白质;表达式;统防;磷酸盐;甘露糖;阳离子;膜;

Luminal/extracellular domains of chimeric CI-M6PR-C proteins interfere with their retrograde endosome-to-TGN trafficking in the transient expression system

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