Our research is focused on role of RNA-binding proteins in axon guidance. During development and regeneration of neural circuits, correct axonal navigation by molecular guidance cues is very important to make precise synaptic connections. A growth cone, the sensory-motile tip of a growing axon, make choices of proper routes for neurite extension and locating correct targets for synapse formation. We propose that mRNA transport and local protein synthesis in growth cones regulated by RNA-binding proteins are important for growth cone motility and axon guidance. Recently, we have shown that beta-actin mRNA and its zipcode binding protein (ZBP1), which binds and rapidly transports beta-actin mRNA in axons to the growth cones, are localized asymmetrically in growth cones in response to local stimulation of a guidance factor. Ongoing research is aimed at understanding the mechanism of ZBP1 to regulate mRNA transport and local protein synthesis of beta-actin for axon guidance.
The second research theme is to investigate the role of the survival motor neuron (SMN) protein, the causal gene product of Spinal Muscular Atrophy (SMA), in axon guidance. SMN is a part of diverse large RNA-protein complexes in all cells, where one well characterize role is to promote small nuclear ribonucleoprotein particle (snRNP) maturation in cell body. However, we hypothesize that localized SMN-mRNP complexes in axons and growth cones are involved in growth cone movement via mRNA transport and/or protein synthesis, and the deficiency of this function in neurons leads to SMA. Our research focuses on how SMN protein functions at the distal tips of axons in response to axon guidance cues. The research would make some contributions to understand the mechanism of onset of this disease.
Name: Yukio Sasaki,
