| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Research Abstract |
Neurite outgrowth is a vital process for neural network formation in which microtubules and actin filaments play major roles. Previous studies with nematode mutants and cultured mammalian neurons revealed that another class of nucleotide-binding protein polymers of septins is also required for neurite outgrowth, besides their implications in mammalian neuronal migration, spine morphogenesis, synaptic transmission, and neuropsychiatric disorders. However, due to the functional redundancy among septin family and their pleiotropic roles, the mechanism of action remains unclear. In this study, we focused on the role of septins in neurite elongation : We cultured neurons from mouse embryonic cerebral cortex and depleted the pivotal subunit SEPT7 by expressing shRNA. Quantitative morphometric analysis demonstrated that SEPT7 depletion inhibited the elongation of both axons and dendrites equally by～30%. To test the physiological relevance of the SEPT7-depletion phenotype found in vitro. We found that the axon extension and branching was significantly diminished in SEPT7-depleted pyramidal neurons. Since microtubule is the common and critical architectural determinant of axon and dendrite, we examined the status of microtubule organization. Intriguingly, septin-depleted neurons contained significantly more acetylated alpha-tubulin, indicating hyperstabilization of microtubules. In this study, we found a novel molecular mechanism connecting septins and microtubule during neurite elongation.
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