Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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Outline of Final Research Achievements |
The aim of this project is to elucidate the molecular and structural mechanisms of CRMP2-regulated axon induction/repulsion. During the neuronal cell development, CRMP2 localizes the tips of the future axon in which CRMP2 forms the hetero-trimer with GTP-tubulin to add tubulins to the plus-ends of microtubules. This effectively induces the axonal microtubule formation, and thus the axon is effectively elongated. On the other hand, phosphorylation of CRMP2 decreases the affinity between CRMP2 and microtubule. It is driven by the small conformational changes at the C-terminal tail of CRMP2 with shifting the surface charges, which not only alter the interactions within the CRMP2 tetramer but also alter the interactions with GTP-tubulin. Consequently, phosphorylated CRMP2 fails to form a hetero-trimer with GTP-tubulin, thus losing the ability to establish and maintain the axonal microtubules.
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