Laboratory for Molecular Membrane Neuroscience
Research Areas
| Healthy neural development and maintenance is dependent upon a reciprocal relationship between glia and neurons. Our laboratory has demonstrated the dependence that neurons have on astroglia in vitro. We showed that hippocampal and cerebellar Purkinje cells in vitro require L-serine, a non-essential amino acid actively released by astroglia, in order to survive and develop. We are continuing to study this novel form of functional coupling between astroglia and neurons, now looking at its role in vivo in a transgenic mouse model. In vitro, exogenous L-serine is taken up into neurons and is used in the synthesis of a particular component of neuronal membranes, called sphingolipids. Neural sphingolipids form an important component of membrane lipid microdomain "rafts", and several recent studies have demonstrated their role in the signal transduction processes of cell apoptosis,survival and differentiation. Our laboratory has cloned the genes that encode key enzymes for the synthesis of sphingolipids, such as ceramide glucosyltransferase (GlcT-1). We are developing both conventional and conditional transgenic mouse strains to study the role of neuronal raft sphingolipids in vivo. |  Laboratory Head Yoshio HIRABAYASHI (Ph.D.)  |
Research Subjects
| (1) | Molecular cellular biology of membrane sphingolipid biosynthesis |
| (2) | Neuron-astroglia interaction required for neuronal survival and development |
| (3) | Molecular cellular biology of lipid rafts and complex carbohydrate |
| (4) | Molecular mechanisms of energy-sensing in multicellular system |
List of Selected Publications
| (1) | Kinoshita, M.O., Furuya, S., Ito, S., Shinoda, Y., Yamazaki, Y., Greimel, P., Ito, Y., Hashikawa, T., Machida, T., Nagatsuka, Y., and Hirabayashi, Y.: "Lipid rafts enriched in phosphatidylglucoside direct astroglial differentiation by regulating tyrosine kinase activity of epidermal growth factor receptors." Biochem J. In Press (2009) |
| (2) | Kohyama-Koganeya, A., Kim, Y., Miura, M., and Hirabayashi, Y.: "Drosophila Bride of sevenless (boss) functions as a glucose-responding receptor: loss of boss causes abnormal sugar and lipid metabolism." Proc Natl Acad Sci U S A. 105(40), 15328-15333 (2008) |
| (3) | Hirabayashi, Y. and Furuya, S.: "Roles of l-serine and sphingolipid synthesis in brain development and neuronal survival." Prog. Lipid Res. 47(3), 188-203 (2008). |
| (4) | Nagatsuka, Y., Horibata, Y., Yamazaki, Y., Kinoshita, M., Shinoda, Y., Hashikawa, T., Koshino, H., Nakamura, T., and Hirabayashi, Y.: "Phosphatidylglucoside exists as a single molecular species with saturated fatty acyl chains in developing astroglial membranes." Biochemistry 45(29), 8742-8750 (2006). |
| (5) | Koganeya, A.K., Sasamura, T., Oshima, E., Suzuki, E., Nishihara, S., Ueda, R., and Hirabayashi, Y.: "Drosophila glucosylceramide synthase: A negative regulator of cell death mediated by proapoptotic factors." J Biol Chem. 279, 35995-36002 (2004) |
| (6) | Yoshida, K., Furuya, S., Osuka, S., Mitoma, J., Shinoda, Y., Watanabe, M., Azuma, N., Tanaka, H., Hashikawa, T., Itohara, S., and Hirabayashi, Y.: "Targeted disruption of the mouse 3-phosphoglycerate dehydrogenase gene causes severe neurodevelopmental defects and results in embryonic lethality." J. Biol. Chem., 279, 3573-3577 (2004). |
| (7) | Nagatsuka, Y., Fujiwara, S., Ohshima, E., Ishii, K., Kobayashi, T., Shimizu, K., and Hirabayashi, Y.: "Carbohydrate-dependent signaling from the phosphatidylglucoside-based microdomain induces granulocytic differentiation of HL60 cells." Proc. Natl. Acad. Sci. USA., 100, 7454-7459 (2003). |
| (8) | Yamazaki, M., Yamada, K., Furuya, S., Mitoma, J., Hirabayashi, Y., and Watanabe, M.: "3- Phosphoglycerate dehydrogenase (3PGDH), a key enzyme for L-serine biosynthesis, is preferentially expressed in the radial glia/ astrocyte lineage and olfactory ensheathing glia in the mouse brain." J. Neuroscience, 21, 7691-7704 (2001). |
| (9) | Furuya, S., Tabata, T., Mitoma, J., Yamada, K., Yamasaki, M., Yamamoto, T., Watanabe, M., Kano, M., and Hirabayashi, Y.: "L-Serine and glycine serve as major astroglia-derived trophic factors for cerebellar Purkinje neurons." Proc. Natl. Acad. Sci. USA, 97, 11528-11533 (2000). |
| (10) | Ichikawa, S. and Hirabayashi, Y.: "Glucosylceramide synthase and glycosphingolipid synthesis." Trends Cell Biol.,(review article)8, 198-202 (1998). |