Research Papers: Gerotarget (Focus on Aging):

CLEC4C p.K210del variant causes impaired cell surface transport in plasmacytoid dendritic cells of amyotrophic lateral sclerosis

Su Min Lim, Young-Eun Kim, Won Jun Choi, Ki-Wook Oh, Min-Young Noh, Min-Soo Kwon, Minyeop Nahm, Namshin Kim, Chang-Seok Ki and Seung Hyun Kim _

PDF  |  HTML  |  How to cite

Oncotarget. 2016; 7:24942-24949. https://doi.org/10.18632/oncotarget.7886

Metrics: PDF 2218 views  |   HTML 2214 views  |   ?  


Su Min Lim1,5,*, Young-Eun Kim2,*, Won Jun Choi3, Ki-Wook Oh4,5, Min-Young Noh5, Min-Soo Kwon6, Minyeop Nahm5, Namshin Kim7, Chang-Seok Ki8,*, Seung Hyun Kim1,4,5,*

1Department of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea

2Green Cross Genome, Yongin, Republic of Korea

3Department of Neurology, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah, United Arab Emirates

4Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea

5Cell Therapy Center, Hanyang University Hospital, Seoul, Republic of Korea

6Department of Pharmacology, School of Medicine, CHA University, CHA Bio Complex, Seongnam, Republic of Korea

7Epigenomics Research Center Genome Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea

8Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

*These authors contributed equally to this work

Correspondence to:

Seung Hyun Kim, email: [email protected]

Chang-Seok Ki, email: [email protected]

Keywords: C-type lectin, whole-exome sequencing, dilysine motif, ER retention, amyotrophic lateral sclerosis, Gerotarget

Received: October 07, 2015     Accepted: January 29, 2016     Published: March 01, 2016


The type II C-type lectin CLEC4C is a transmembrane protein selectively expressed on plasmacytoid dendritic cells (PDCs). Although its mechanism of action remains unclear, triggering of the extracellular C-terminal C-type carbohydrate recognition region of CLEC4C regulates the secretion of proinflammatory cytokines and type I IFNs in PDCs. Applying whole-exome sequencing in a patient with juvenile amyotrophic lateral sclerosis (ALS) and both healthy parents, we identified a de novo CLEC4C variant (c.629_631delAGA; p.Lys210del). In this study, we report that the deletion of a lysine residue at the extracellular region of CLEC4C yields a C-terminal dilysine motif that results in endoplasmic reticulum (ER) retention of the protein in transfected HeLa and Jurkat T lymphoma cell models. As a consequence, a decrease in the surface expression of CLEC4C and the ER localization of the mutant construct were observed. Furthermore, depletion of the cell surface CLEC4C level was also observed in the patient PDCs, further suggesting that the variant p.Lys210del CLEC4C may contribute to juvenile ALS susceptibility.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 7886