Expression of Functionally Different Dectin-1 Isoforms by Murine Macrophages
Document Type
Article
Publication Date
5-1-2006
Description
Dectin-1 is a specific receptor for β-glucans and a major receptor for fungal particles on macrophages (Mφ). It is a type II membrane receptor that has a C-terminal, NK-like, C-type lectin-like domain separated from the cell membrane by a short stalk region and a cytoplasmic immunoreceptor tyrosine-based activation-like motif. We observed functional differences in dectin-1-dependent recognition of fungal particles by Mφ from different mouse strains. RT-PCR analysis revealed that mice have at least two splice forms of dectin-1, generated by differential usage of exon 3, encoding the full-length dectin-1A and a stalkless Mφ dectin-1B. Mφ from BALB/c mice and genetically related mice expressed both isoforms in similar amounts, whereas Mφ from C57BL/6 and related mice mainly expressed the smaller isoform. NIH-3T3 fibroblast and RAW264.7 macrophage cell lines stably expressing either isoform were able to bind and phagocytose zymosan at 37°C. However, binding by the smaller dectin-1B isoform was significantly affected at lower temperatures. These properties were shared by the equivalent human isoforms. The relative ability of each of the isoforms to induce TNF-α production in RAW264.7 Mφ was also found to be different. These results are the first evidence that dectin-1 isoforms are functionally distinct and indicate that differential isoform usage may represent a mechanism of regulating cellular responses to β-glucans.
Citation Information
Heinsbroek, Sigrid; Taylor, Philip R.; Rosas, Marcela; Willment, Janet A.; Williams, David L.; Gordon, Siamon; and Brown, Gordon D.. 2006. Expression of Functionally Different Dectin-1 Isoforms by Murine Macrophages. Journal of Immunology. Vol.176(9). 5513-5518. https://doi.org/10.4049/jimmunol.176.9.5513 PMID: 16622020 ISSN: 0022-1767