Fig. 8

Schematic diagram depicts the role of SCUBE3 in enhancing the BMP signaling critical for endochondral bone formation. A When SCUBE3 (+/+) is present, it facilitates BMP2/4 ligand binding to type II receptors (BMPR-II) and recruits BMP type I receptors (BMPRIA or BMPRIB) to generate a SCUBE3-enhanced signaling complex. This complex relocates to the lipid raft (green-colored area) in response to BMP stimulation, which increases activation of the signaling cascade required for concerted endochondral bone formation. B In the absence of SCUBE3, lipid rafts show reduced BMP2 and BMP receptor levels. Thus, BMP downstream signaling and function are attenuated. Scube3 deficiency in mice results in short stature, short-limbed skeletal dysplasia, misalignment of the front teeth, and kinked tail. In addition, bone mineral density is markedly lower in Scube3-deficient (−/−) mice compared to controls