| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
1. Follistatin-related protein (FRP, TSC-36), a follistatin domain-containing protein was originally isolated as a cDNA that was up-regulated by TGF-β in mouse osteogenic MC3T3E1 cells. We have isolated a homologue (xFRP) of the cDNA from Xenopus laevis to clarify the function in early embryogenesis. In the Xenopus embryos, xFRP mRNA expression started at the onset of gastrulation, and sustained through the tail-bud stage. The mRNAs Were localized in the Spemann organizer, notochord, neural floor plate, hypochord and somite. The similarities with the pattern of expression of Xenopus follistain mRNA suggests that xFRP may play a role in neuralization. Follistatin is an activin-binding protein and binds to heparin/heparansulfate carbohydrate moieties on the cell surface proteoglycans. Thus, a function of follistain on the neuralization may be performed by the inhibition of activin actions. We have also found that follistatin can mediate the activin metabolization after the internalization via surface heparansulfate-proteoglycans in various cultured cell lines.
2. We have identified a mouse PDZ protein that interacts with the activin type IIA receptor (ActRIIA), which we named activin receptor-interacting protein 1 (ARIP1). ARlP1 had one guanylate kinase domain in the NH(2)-terminal region, followed by two WW domains and five PDZ domains (PDZ1-5), and interacted with ActRIIA through PDZ5. ARIP1 interacts specifically with ActRIIA among the receptors for the transforming growth factor beta family. Interestingly, ARIP1 also interacted with Smad3, which is an activin/transforming growth factor beta intracellular signaling molecule. The mRNA of ARIPI was more abundant in the brain than in other tissues. These findings suggest that ARIP1 has a significant role in assembling activin signaling molecules at specific subcellular sites and in regulating signal transduction in neuronal cells.
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