title: Expression of functionally different dectin-1 isoforms by murine macrophages.
abstract: 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.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors.forename: Sigrid E M
authors.initials: SE
authors.lastname: Heinsbroek
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Marcela
authors.initials: M
authors.lastname: Rosas
authors.forename: Janet A
authors.initials: JA
authors.lastname: Willment
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D037181:Lectins, C-Type; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000145:classification / Q000235:genetics / Q000378:metabolism; D013696:Temperature; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015054:Zymosan / Q000378:metabolism; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan; D000099181:Dectin-1