| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
|
|---|
| Research Abstract |
Neurite outgrowth is a vital process for neural network formation in which microtubules and actin filaments play major roles. Previous studies revealed that another class of nucleotide-binding protein polymers of septins is also required for neurite outgrowth. However, the mechanism are unclear. Here we found that depletion of the pivotal septin subunit SEPT7 from cerebrocortical neurons causes hyperacetylation of microtubules and inhibits the outgrowth of both axons and dendrites. The phenotypic similarity between SEPT7 depletion and inhibition of the major tubulin deacetylase HDAC6 allowed the detection of their functional and physical interactions. While HDAC6–acetylated tubulin interaction is unaffected by the association of septins, it is significantly diminished in SEPT7-depleted neurons. These data suggest a novel molecular network in which septins facilitate HDAC6-mediated tubulin deacetylation, thus optimizing microtubule dynamics for neurite outgrowth.
|
