Functional analyses of a seven transmembrane receptor essential for osteoclast differentiation

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Osteoclasts are bone-resorbing, multinucleated giant cells that are essential for bone remodeling and are formed through cell fusion of mononuclear precursor cells. By cDNA subtraction, we previously isolated a cDNA clone coding for seven-transmembrane receptor DC-STAMP which plays an important role in ostc oclastogenesis (Kukita et al. J. Exp. Med. 200:941, 2004). In order to reveal the function of DC-STAMP, we have tried to identify its ligand using several methods and a mouse cell line which differentiates into osteoclast-like cells upon stimulation. However, positive results have not been obtained so far.Since the zebrafish draft genome sequence does not contain the DC-STAMP gene sequence, we have not been able to do the knock-down experiment. However, we found by database search a novel gene with sequence homology to a portion of the DC-STAMP gene. There are 3 genes containing this DC-STAMP motif in the zebrafish genome. We isolated a cDNA for one of the genes based on the EST data. This gene contains transmembrane regions and may be involved in the cell fusion like DC-STAMP. Recently Drosophila Snky and C. elegans Spe-42 proteins have been shown to have the DC-STAMP motif, although the orthologous relationships with the zebrafish gene are unclear. These transmembrane proteins are shown to be required in egg-sperm membrane fusion. Therefore analyses of the zebrafish genes with the DC-STAMP motifs will provide additional insights into the mechanisms involved in the membrane fusion.