Characterization of Alternatively Spliced Transcript Variants of CLEC2D Gene

Lectin-like transcript 1 (LLT1) encoded by CLEC2D gene is a C-type lectin-like molecule interacting with human CD161 (NKR-P1A) receptor expressed by natural killer cells and subsets of T cells. Using RT-PCR and sequencing, we identified several CLEC2D alternatively spliced transcript variants genera...

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Bibliographic Details
Published in:	The Journal of biological chemistry Vol. 285; no. 46; pp. 36207 - 36215
Main Authors:	Germain, Claire, Bihl, Franck, Zahn, Stefan, Poupon, Gwenola, Dumaurier, Marie-Jeanne, Rampanarivo, Hariniaina Henintsoa, Padkjær, Søren Berg, Spee, Pieter, Braud, Veronique M.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 12-11-2010 American Society for Biochemistry and Molecular Biology
Subjects:	Alternative Splicing Amino Acid Sequence Animals Base Sequence Blotting, Western Cell Line, Tumor Cell Surface Receptor Cells, Cultured Endoplasmic Reticulum Endoplasmic Reticulum - metabolism Gene Expression Gene Expression Profiling HEK293 Cells Humans Immunology Jurkat Cells Lectins, C-Type Lectins, C-Type - chemistry Lectins, C-Type - genetics Lectins, C-Type - metabolism Life Sciences Lymphocyte MHC Mice Models, Molecular Molecular Sequence Data NK Cell Lectin-Like Receptor Subfamily B NK Cell Lectin-Like Receptor Subfamily B - chemistry NK Cell Lectin-Like Receptor Subfamily B - genetics NK Cell Lectin-Like Receptor Subfamily B - metabolism Protein Binding Protein Isoforms Protein Isoforms - chemistry Protein Isoforms - genetics Protein Isoforms - metabolism Protein Multimerization Receptors, Cell Surface Receptors, Cell Surface - chemistry Receptors, Cell Surface - genetics Receptors, Cell Surface - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger RNA, Messenger - genetics RNA, Messenger - metabolism Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Transcription, Genetic Transcription, Genetic - genetics MHC Gene Expression Immunology Cell Surface Receptor Lymphocyte
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Summary:	Lectin-like transcript 1 (LLT1) encoded by CLEC2D gene is a C-type lectin-like molecule interacting with human CD161 (NKR-P1A) receptor expressed by natural killer cells and subsets of T cells. Using RT-PCR and sequencing, we identified several CLEC2D alternatively spliced transcript variants generated by exon skipping. In addition to the reported transcript variants 1 (LLT1) and 2, we identified a novel splice variant 4 and transcripts coding for putative soluble proteins. CLEC2D transcripts were detected primarily in hematopoietic cell lines and were found to be co-induced by the same activation signals. Although very low amounts of putative soluble CLEC2D protein isoforms could be produced by transfectants, CLEC2D isoforms 2 and 4 were efficiently expressed. By contrast to LLT1, which was detected on the cell surface, isoform 2 and 4 remained in the endoplasmic reticulum where they formed homodimers or heterodimers with LLT1. They failed to interact with CD161, leaving LLT1 as the sole ligand for this receptor. CLEC2D therefore uses gene splicing to generate protein isoforms that are structurally distinct and that have different biological activities.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 PMCID: PMC2975243
ISSN:	0021-9258 1083-351X
DOI:	10.1074/jbc.M110.179622