| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Outline of Final Research Achievements |
The NELL1 gene was originally identified in craniosynostosis patients as being specifically unregulated within prematurely fusing sutures. Because of its potent osteoinductive activity, NELL1 protein may be useful for bone regeneration therapy. However, there is little knowledge regarding NELL1 receptors and NELL1-mediated signaling pathways. In this study, we demonstrate that NELL1 binds to cell surface proteoglycans through its thrombospondin-1 N-terminal (TSPN) domain. Major heparin-binding sites were identified on the three-dimensional structural model of the TSPN domain of NELL1. Mutant analysis of the heparin-binding sites indicated that the heparin-binding activity of the TSPN domain is involved in interaction of NELL1 with cell surface proteoglycans. We also found that NELL1 binds to Robo3 receptor through its EGF-like repeats.
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