| Research Abstract |
I have proposed a hypothesis that diversity of neural plasticity is regulated by post-translational modification of proteins. I have focused on extracellular serine protease in brain and have investigated on roles of proteolysis in neural plasticity in vivo and in vitro. Especially, S1 (clan SA) serine protease neuropsin expresses in the hippocampus and the amygdaloid complex and affects long-term potentiation (LTP) in the hippocampus slices, proposing that finding the function of neuropsin in brain could lead to know neural plasticity. Furthermore, I have proposed that regulation of neuropsin activity by the specific inhibitor is required to protect the valance of brain functions. During this grand, paper showing that Serpinhb6 is the specific inhibitor of neuropsin in brain was published. Then I compared distribution of Serpinb6 mRNA and the end-product with that of neuropsin mRNA in brain. As results, expression of neuropsin was covered by expression of Serpinb6 in brain completely.
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And Serpinb6 expressed also in brain area without neuropsin, suggesting the presence of new protease inhibited by Serpinb6. These results were also published in 2002. Alternatively, we investigated role of loop structures of neuropsin in the activity of serine protease and regulated secretion. Little, so far, is known about the roles of loops in members of the S1 (clan SA) family of serine proteases. The loops include those stabilized by six disulfide bonds or a loop C (Gly^<69>-Glu^<80>) and an N-glycosylated kallikrein loop (His^<91>-Ile^<103>) not containing a site linked by a disulfide bond. First, among the six disulfide bonds, only SS1 in loop E (Gly^<142>-Leu^<155>) and SS6 in loop G (Ser^<185>-Gly^<197>) were necessary for the catalytic efficiency of neuropsin. Second, disruptions of loop C and the N-linked oligosaccharide chain on the kallikrein loop affected the catalytic efficiency and P2 specificity, respectively. Furthermore, disruptions of loop C and the kallikrein loop enhanced the regulated secretion. Finally, the present results were published and provided new information on the structure-function of family S1 (clan SA) serine protease. Less
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