Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Outline of Final Research Achievements |
The objective of this study was to determine the signaling pathway in which PTPRZ, a receptor-type tyrosine phosphates, enhances context fear memory formation, and methamphetamine-induced place preference. We found that phosphorylation of GIT1 at tyrosine residue 554 was higher in the synaptosomes obtained from Ptprz-deficient mice than in those from wild-type mice. We also revealed that GIT1 dephosphorylation by PTPRZ was essential for the normal GIT1 function. These new findings suggest that the regulation of GIT1 by PTPRZ in central synapses leads to undesirable learning outcomes in the fear memory consolidation (the animal model of post-traumatic stress disorder), and drug addiction. Unfortunately, we failed to develop a cell permeable pseudosubstrate PTPRZ inhibitor, and therefore the in vivo effect of pharmacological PTPRZ inhibition could not be examined.
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