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Each human body is composed of tissues and organs which are made up of cells, amounting to thousands of billions of cells per body. Life is maintained by linkage of these components. Cells communicate with each other by means of hormones, neurotransmitters, cell growth and differentiation factors which induce a variety of cellular responses. Signal transduction pathways before responses form complex networks. In some disease, disturbances of the signal transduction systems are found. A number of drugs targeted at some particular molecules of the signal transduction system are used for the treatment of such disease. Our laboratory is engaged in clarification of the molecular mechanisms of responses of cells to signals, identification of the etiology of neurological diseases, cancers and other disease and research on treatment of such disease.
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1 ) Signal transduction mediated by G protein-coupled receptor
Trimeric GTP-bound protein composed of 3 subunits (α, β and γ), i.e. G-protein, is activated by G protein-coupled receptor containing seven transmembrane segments, to serve as a transducer which transmits signals into cells. The signals mediated by G protein are indispensable for various systems which coordinate the living body such as the nerve system, the endocrine and metabolic system, the immune system and the development system. However, there are many open questions pertaining to the mechanism for regulation of G protein signals and their physiological functions. We attempt to contribute to advancing creation of drugs targeted at components of G protein signals through identification of unknown molecules involved in regulation of G protein signals and analyzing their function.
2 ) Mechanisms for regulation of self-renewal, differentiation and migration of neural stem cells
Neural stem cells which can differentiate into both neuron and glia are found not only in fetuses but also in mature organisms. However, the mechanism for self-renewal, determination of the fate of differentiation, asymmetric cell division, migration and so on of these cells involves many unresolved questions. Using cultures of neural stem cells which form neurospheres and cultures of brain slices, we attempt to resolve the above-mentioned questions from the standpoint of signal transduction mechanisms.
3 ) Molecular mechanisms for neuronal network formation in brain
In the brain, neurons work as if they were semi-conductors constituting a computer. For this function, the polarity of neurons is important. Each neuron has a single axon and multiple dendrites. The dendrites receive signals which are then dispatched from the axonal ending. As a result, the flow of signals in the neurons is directed from the dendrites to the axon. Then, how does the neuron form the axon and dendrite to acquire polarity? We attempt to clarify this issue at the molecular level by means of proteome analysis, making full use of high-resolution two-dimensional gel electrophoresis.
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- Toriyama M. et al., J. Cell Biol., 175, 147-157, 2007
- Mizuno N. et al., Proc. Natl. Acad. Sci. USA, 102, 12365-12370, 2005
- Miyamoto Y. et al., J. Biol. Chem., 279, 34336-34342, 2004
- Miyamoto Y. et al., J. Biol. Chem., 278, 29890-29900, 2003
- Inagaki N. et al., Nature Neurosci., 4, 781-782, 2001
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Fig. 1 Signal transduction mediated by G protein-coupled receptor
Fig. 2 Neuron (red), astrocyte (blue) and oligodendrocyte (green) differentiating from neural stem cells
Fig. 3 Polarity of neurons and the flow of signals
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