Expression of functionally different dectin-1 isoforms by murine macrophages.

Journal article

Dectin-1 is a specific receptor for beta-glucans and a major receptor for fungal particles on macrophages (Mphi). 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 Mphi 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 Mphi dectin-1B. Mphi from BALB/c mice and genetically related mice expressed both isoforms in similar amounts, whereas Mphi 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 degrees 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-alpha production in RAW264.7 Mphi 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 beta-glucans.

Authors: Heinsbroek, SE; Taylor, P; Rosas, M; Willment, J; Williams, D

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 176
• Issue: 9
• Pages: 5513-5518
• Publication date: 2006-05-01
• DOI: 10.4049/jimmunol.176.9.5513
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Gene Expression Regulation; Lectins, C-Type; Humans; Zymosan; Tumor Necrosis Factor-alpha; Macrophages; Membrane Proteins; Protein Isoforms; Nerve Tissue Proteins; Mice; Temperature; Cell Line; Animals