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KDEL receptor is a cell surface receptor that cycles between the plasma membrane and the Golgi via clathrin-mediated transport carriers

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Abstract

KDEL receptor cycles between the ER and the Golgi to retrieve ER-resident chaperones that get leaked to the secretory pathway during protein export from the ER. Recent studies have shown that a fraction of KDEL receptor may reside in the plasma membrane and function as a putative cell surface receptor. However, the trafficking itinerary and mechanism of cell surface expressed KDEL receptor remains largely unknown. In this study, we used N-terminally Halo-tagged KDEL receptor to investigate its endocytosis from the plasma membrane and trafficking itinerary of the endocytosed receptor through the endolysosomal compartments. Our results indicate that surface-expressed KDEL receptor undergoes highly complex recycling pathways via the Golgi and peri-nuclear recycling endosomes that are positive for Rab11 and Rab14, respectively. Unexpectedly, KDEL receptor appears to preferentially utilize clathrin-mediated endocytic pathway as well as clathrin-dependent transport carriers for export from the trans-Golgi network. Taken together, we suggest that KDEL receptor may be a bona fide cell surface receptor with a complex, yet well-defined trafficking itinerary through the endolysosomal compartments.

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Funding

This project was sponsored by Shanghai Pujiang Program (16PJ1407 to YQ). Financial support of this study was provided exclusively by the ShanghaiTech University.

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Author notes

  1. Jie Jia and Xihua Yue contributed equally to this work.

Authors and Affiliations

  1. School of Life Science and Technology, ShanghaiTech University, Pudong, Shanghai, China

    Jie Jia, Xihua Yue, Lianhui Zhu, Shuaiyang Jing, Yijing Wang, Yi Qian & Intaek Lee

  2. School of Physical Science and Technology, ShanghaiTech University, Pudong, Shanghai, China

    Bopil Gim

  3. University of Chinese Academy of Sciences, Beijing, China

    Jie Jia, Shuaiyang Jing & Yijing Wang

Authors
  1. Jie Jia
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  2. Xihua Yue
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  3. Lianhui Zhu
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  4. Shuaiyang Jing
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  5. Yijing Wang
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  6. Bopil Gim
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  7. Yi Qian
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  8. Intaek Lee
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Contributions

IL, XY, YQ designed the study. JJ, XY, YQ, LZ, BG, SJ, YW performed the experiments. JJ, XY, YQ and IL wrote the manuscript.

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Correspondence to Yi Qian or Intaek Lee.

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18_2020_3570_MOESM1_ESM.pdf

Supplementary file1. Supplementary Fig. 1(A) KDELR1 knockdown efficiency in MCF7 KDELR KD cells was determined by quantitative real-time PCR in three independent experiments and summarized by histogram. KDELR2 and KDELR3 mRNA levels were also determined as controls. Y axis indicates the relative mRNA level of KDEL receptor in MCF7 KDELR KD cells compared to MCF7 control cells. **: P < 0.01 (B) KDELR1 protein knockdown efficiency by siRNA was determined. KDELR1-3Flag-mCherry knock-in cells were transfected with scramble or KDELR1 siRNA for 72 h before lysed and analyzed by western blotting with anti-mCherry and anti-GAPDH antibodies. Supplementary Fig. 2(H) Confocal images of overexpressed Halo-KDELR or Halo-KDELR H12A in the Golgi region of HeLa cells. Endogenous GM130 was stained as a Golgi marker. Scale bar: 1 µm. Bar graph summarize the co-localization of Halo-KDELRs with GM130 (n = 15 cells). ns not significant. Statistical analysis was performed using Students’ t test. Supplementary Table 1. Summary of the Pearson coefficient values (mean ± SD) in the graphs (PDF 134 kb)

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Jia, J., Yue, X., Zhu, L. et al. KDEL receptor is a cell surface receptor that cycles between the plasma membrane and the Golgi via clathrin-mediated transport carriers. Cell. Mol. Life Sci. 78, 1085–1100 (2021). https://doi.org/10.1007/s00018-020-03570-3

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  • DOI: https://doi.org/10.1007/s00018-020-03570-3

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