Absence of a human ortholog of rodent Kupffer cell galactose-binding receptor encoded by the CLEC4f gene
File(s)
Published version
Author(s)
Taylor, Maureen
Snelling, Tom
Smith, David F
Drickamer, Kurt
Type
Journal Article
Abstract
The murine CLEC4f gene encodes the Kupffer cell receptor, a galactose-binding receptor containing a C-type carbohydrate-recognition domain. Orthologs have been identified in nearly 100 species. The receptors from rat and mouse have previously been characterized and data presented here show that functional CLEC4f protein is expressed in domestic cattle (Bos taurus). However, the human CLEC4f gene does not encode a functional receptor because a mutation in the splice acceptor site of the final exon prevents appropriate splicing and a missense mutation disrupts the sugar-binding site. Transcriptomic and PCR analysis of transcripts confirms the absence of a spliced transcript containing the final exon and only background levels of transcripts are detected in human tissues. These mutations are also present in the CLEC4f gene in Neanderthals. In contrast to humans, closely related species, including chimpanzees, do have CLEC4f genes that encode full-length receptors. Affinity chromatography and glycan array results demonstrate that the chimpanzee, bovine and murine proteins all bind to galactose, but they show preferences for different subsets of galactose-containing glycans. In non-human primates, the receptor is expressed in spleen rather than in liver. The results indicate that the CLEC4f protein probably has distinct functions in different species. Absence of the receptor precludes using it for targeting of glycoconjugates to cells in human liver. The fact that CLEC4f protein is expressed in spleen in non-human primates and the close evolutionary relationship of the CLEC4f protein to langerin (CD207) suggest that it may function in the immune system, possibly as a pathogen receptor.
Date Issued
2019-04-01
Date Acceptance
2018-12-20
Citation
Glycobiology, 2019, 29 (4), pp.332-345
ISSN
0959-6658
Publisher
Oxford University Press (OUP)
Start Page
332
End Page
345
Journal / Book Title
Glycobiology
Volume
29
Issue
4
Copyright Statement
© 2019 The Author(s). Published by Oxford University Press.1This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permitsunrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor
Wellcome Trust
Biotechnology and Biological Sciences Research Council (BBSRC)
Grant Number
093599/Z/10/Z
BB/P005659/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
evolution
glycan array
glycan-binding receptor
lectin
transcriptomics
FUCOSE-CONTAINING GLYCOPROTEINS
HEPATIC LECTINS
GLYCAN ARRAY
IDENTIFICATION
EXPRESSION
CLEARANCE
SEQUENCE
EPITOPE
DNA
evolution
glycan array
glycan-binding receptor
lectin
transcriptomics
Animals
Humans
Kupffer Cells
Lectins, C-Type
Mice
Receptors, Cell Surface
Biochemistry & Molecular Biology
11 Medical and Health Sciences
06 Biological Sciences
Publication Status
Published
Date Publish Online
2018-12-24