CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation

DH Chung, MB Humphrey, MC Nakamura… - The Journal of …, 2003 - journals.aai.org
DH Chung, MB Humphrey, MC Nakamura, DG Ginzinger, WE Seaman, MR Daws
The Journal of Immunology, 2003journals.aai.org
By homology to triggering receptor expressed by myeloid cells-2, we screened the mouse
expressed sequence tag database and isolated a new single Ig domain receptor, which we
have expressed and characterized. The receptor is most similar in sequence to the human
CMRF-35 receptor, and thus we have named it CMRF-35-like molecule (CLM)-1. By
screening the mouse genome, we determined that CLM-1 was part of a multigene family
located on a small segment of mouse chromosome 11. Each contains a single Ig domain …
Abstract
By homology to triggering receptor expressed by myeloid cells-2, we screened the mouse expressed sequence tag database and isolated a new single Ig domain receptor, which we have expressed and characterized. The receptor is most similar in sequence to the human CMRF-35 receptor, and thus we have named it CMRF-35-like molecule (CLM)-1. By screening the mouse genome, we determined that CLM-1 was part of a multigene family located on a small segment of mouse chromosome 11. Each contains a single Ig domain, and they are expressed mainly in cells of the myeloid lineage. CLM-1 contains multiple cytoplasmic tyrosine residues, including two that lie in consensus immunoreceptor tyrosine-based inhibitory motifs, and we demonstrate that CLM-1 can associate with Src-homology 2 containing phosphatase-1. Expression of CLM-1 mRNA is down-regulated by treatment with receptor activator of NF-κB ligand (RANKL), a cytokine that drives osteoclast formation. Furthermore, expression of CLM-1 in the osteoclastogenic cell line RAW (RAW. CLM-1) prevents osteoclastogenesis induced by RANKL and TGF-β. RAW. CLM-1 cells fail to multinucleate and do not up-regulate calcitonin receptor, but they express tartrate-resistant acid phosphatase, cathepsin K, and β 3 integrin, suggesting that osteoclastogenesis is blocked at a late-intermediate stage. Thus, we define a new family of myeloid receptors, and demonstrate that the first member of this family, CLM-1, is an inhibitory receptor, able to block osteoclastogenesis.
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