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

• Published in: Cellular and molecular life sciences : CMLS 2021-02, Vol.78 (3), p.1085-1100
• Main Authors: Jia, Jie, Yue, Xihua, Zhu, Lianhui, Jing, Shuaiyang, Wang, Yijing, Gim, Bopil, Qian, Yi, Lee, Intaek
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Line, Tumor; Cell Membrane - metabolism; Cell surface; Chaperones; Clathrin; Clathrin - metabolism; Compartments; Endocytosis; Endosomes; Endosomes - metabolism; Exports; Gene Editing; Golgi apparatus; Golgi Apparatus - metabolism; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Life Sciences; Membrane trafficking; Membranes; Microscopy, Fluorescence; Mutagenesis, Site-Directed; Original; Original Article; Peptides; Plasma; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein transport; Protein turnover; Proteins; rab GTP-Binding Proteins - metabolism; Receptors; Receptors, Peptide - antagonists & inhibitors; Receptors, Peptide - genetics; Receptors, Peptide - metabolism; RNA Interference; RNA, Small Interfering - metabolism
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-020-03570-3

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.