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

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Title
CLEC4C p.K210del variant causes impaired cell surface transport in plasmacytoid dendritic cells of amyotrophic lateral sclerosis
Author(s)
S M Lim; Y E Kim; W J Choi; K W Oh; M Y Noh; M S Kwon; M Nahm; Namshin Kim; C S Ki; S H Kim
Bibliographic Citation
Oncotarget, vol. 7, no. 18, pp. 24942-24949
Publication Year
2016
Abstract
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.
Keyword
C-type lectinDilysine motifEr retentionAmyotrophic lateral sclerosisWhole-exome sequencing
ISSN
1949-2553
Publisher
Impact Journals
DOI
http://dx.doi.org/10.18632/oncotarget.7886
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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