| First Author | Inui M | Year | 2009 |
| Journal | Proc Natl Acad Sci U S A | Volume | 106 |
| Issue | 12 | Pages | 4816-21 |
| PubMed ID | 19251634 | Mgi Jnum | J:147155 |
| Mgi Id | MGI:3839503 | Doi | 10.1073/pnas.0900463106 |
| Citation | Inui M, et al. (2009) Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis in cooperation with DAP12. Proc Natl Acad Sci U S A 106(12):4816-21 |
| abstractText | Osteoclasts, cells of myeloid lineage, play a unique role in bone resorption, maintaining skeletal homeostasis in concert with bone-producing osteoblasts. Osteoclast development and maturation (osteoclastogenesis) is driven by receptor activator of NF-kappaB ligand and macrophage-colony stimulating factor and invariably requires a signal initiated by immunoreceptor tyrosine-based activation motif (ITAM)-harboring Fc receptor common gamma chain or DNAX-activating protein (DAP)12 (also referred to as KARAP or TYROBP) that associates with the cognate immunoreceptors. Here, we show that a third adaptor, YINM costimulatory motif-harboring DAP10, triggers osteoclastogenesis and bone remodeling. DAP10-deficient (DAP10(-/-)) mice become osteopetrotic with age, concomitant with a reduction in osteoclasts. The DAP10-associating receptor was identified as myeloid DAP12-associating lectin-1 (MDL-1), whose physiologic function has not been found. MDL-1-mediated stimulation of osteoclast precursor cells resulted in augmented osteoclastogenesis in vitro. MDL-1 associates with both DAP12 and DAP10 in osteoclasts and bone marrow-derived macrophages, where DAP10 association depends almost entirely on DAP12, suggesting a formation of MDL-1-DAP12/DAP10 trimolecular complexes harboring ITAM/YINM stimulatory/costimulatory motifs within a complex that could be a novel therapeutic target for skeletal and inflammatory diseases. |
