Regulatory mechanisms underlying neuronal polarization

2015 Fiscal Year Final Research Report

• Project/Area Number: 26830045
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Nagoya University
• Principal Investigator: Tetsuya Takano 名古屋大学, 医学(系)研究科(研究院), 研究員 (00725541)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: Neuronal polarity / RhoA / Rho-kinase / CaMKI

Outline of Final Research Achievements

Neurons are highly polarized cells, which have two structurally and functionally distinct compartments, ie., axons and dendrites. Neuronal polarization is precisely established by local activation signal and long-range inhibitory signaling (Takano et al., 2015, Development). However, the long-range inhibitory signaling that prevents multiple axonal formation remains largely unknown.
In this year, we found that local application of NT-3 to axon induced a long-range Ca2+ propagation that led to activate RhoA in the cell body through CaMKI. The local inhibition of Rho-kinase in the minor neurites induced neurite elongation and subsequently formed multiple axons. We performed phospho-proteomic analysis (the KISS method) to identify novel substrates for CaMKI. We found that CaMKI phosphorylated a RhoGEF, and enhanced its GEF activity. Together, long-range signaling of Ca2+/CaMKI/RhoGEF/RhoA/Rho-kinase might be a novel inhibitory pathway responsible for neuronal polarization.

Free Research Field

神経化学