Neurochemistry and Molecular Cell Biology

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1.Research Summary

In the field of neurochemistry, members in our department (Department of Neurochemistry and Molecular Cell Biology) are studying the principles of three significant events in neuroscience: “formation of the brain (how the neural network is formed),” “expression of brain functions (how the neural network acts),” and “repair of the brain damage (whether the neural network can be regenerated)” based on the interactions among proteins. We are studying the molecular principles common to non-nervous systems from the aspects of vesicular traffic, the cytoskeletal rearrangement, and protein phosphorylation.

2.Research Subjects

A. Analysis of the growth cone functions based on the novel molecular pathways

1) Identification of the protein phosphorylation crucial to the growth cone behavior, revealed by phosphoproteomics
2) Visualization of the vesicular trafficking associated with the growth cone functions
3) Analysis of new signaling pathways in the neuronal polarization

B. Analysis of the mice lacking in the key enzymes for chondroitin sulfate (CS) synthesis

1) Roles of perineuronal nets (PNN) for the synaptic plasticity from the molecular aspects
2) The significance of CS for nerve growth and development
3) CS Functions in multi-organs and pathogenesis of the human diseases as a mouse model

3.Research Results

[Area] Growth cone

[Research subject]

Visualization of the vesicular trafficking associated with the growth cone functions

[Description]
There are many vesicles in the growth cone, however, their roles in nerve growth are not known. We have found the vesicular proteins revealed by proteomics, and succeeded in analyzing their behaviors by superresolutional imaging. Namely, we have discovered the novel interactions between vesicles and dynamics of F-actins, indicating that there is a coordination mechanism between the membrane and the cytoskeleton for nerve growth.

[Photographs]

Photographs

[Area] Chondroitin sulfate

[Research subject]

Efficient repair mechanism of spinal code injury

[Description]
Chondroitin sulfate (CS) is the most abundant inhibitory molecule in the growth cone and in nerve growth/axon regeneration. We produced CSGalNAcT1 (the key enzyme for CS synthesis)-KO mice, and these mice showed remarkable recovery from spinal cord injury. We have discovered the mechanism that optimizes the synthetic balance of glycosaminoglycans for axon regeneration.

[Photographs]

Photographs

Increased regenerating axons in CSGalNAcT1-KO

[Area] Growth cone

[Research subject]

Analysis of new signaling pathways in the neuronal polarization

[Description]
We revealed by proteomics that GPM6a is a membrane protein enriched in the growth cone. The physiological role of this protein is not known. We have recently demonstrated that GPM6a accelerates the neuronal polarization in response to the extracellular signals such as laminin. We have also determined the downstream signaling pathways of GPM6a at a rapid polarization.

[Photographs]

Photographs

The polarized distribution of GPM6a in the neuron cultured on laminin (LN)

Please see the Neurochemistry and Molecular Cell Biology website for a detailed description of our research.

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