Laboratory for Molecular Membrane Neuroscience
Laboratory Head
Yoshio HIRABAYASHI (Ph.D.)
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. We currently discovered a new type of membrane glycolipid, phosphatidylglucoside (PtdGlc), in the CNS. PtdGlc consists solely of saturated fatty acyl chains, denoting its localization in lipid rafts. We are now determining how the glycolipid is biosynthesized, and what the biological functions it might serve. In 2008, we identified BOSS (a putative Drosophila orphan GPCR) as glucose-responding membrane receptor. We now try to understand the biological roles of BOSS/GPRC5 (mammalian orthologue for BOSS) in the central nervous systems using genetically modified animals.
- Molecular cellular biology of membrane sphingolipid biosynthesis
- Neuron-astroglia interaction required for neuronal survival and development
- Molecular cellular biology of lipid rafts and complex carbohydrate
- Molecular mechanisms of energy-sensing in multicellular system
- September 23, 2008
- Identifying a cellular membrane receptor responsive to glucose which is involved in the maintenance of energy homeostasis
- March 13, 2009
- Finding the sweet spot
- Watanabe S., Endo S., Oshima E., Hoshi T., Higashi H., Yamada K., Tohyama K., Yamashita T., Hirabayashi Y.:
" Glycosphingolipid synthesis in cerebellar purkinje neurons: Roles in myelin formation and axonal homeostasis"
Glia, 58, 10, 1197--1207 (2010) - Ayako Kohyama-Koganeya, Yeon-Jeong Kim, Masayuki Miura, Yoshio Hirabayashi.:
" 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) - Hirabayashi Y, Furuya S.:
" Roles of l-serine and sphingolipid synthesis in brain development and neuronal survival"
Prog. Lipid Res. 47(3), 188-203 (2008). - Nagatsuka Y, Horibata Y, Yamazaki Y, Kinoshita M, Shinoda Y, Hashikawa T, Koshino H, Nakamura T, Hirabayashi Y.:
" Phosphatidylglucoside exists as a single molecular species with saturated fatty acyl chains in developing astroglial membranes"
Biochemistry 45(29), 8742-8750 (2006). - Koganeya AK, Sasamura T, Oshima E, Suzuki E, Nishihara S, Ueda R, Hirabayashi Y.:
" Drosophila glucosylceramide synthase: A negative regulator of cell death mediated by proapoptotic factors."
J Biol Chem. 279, 35995-36002 (2004) - 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). - 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). - 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). - 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). - Ichikawa, S. and Hirabayashi, Y.:
" Glucosylceramide synthase and glycosphingolipid synthesis"
Trends Cell Biol.,(review article)8, 198-202 (1998).
Principal Investigator
- Yoshio HIRABAYASHI
- Laboratory Head
Members
- Yeon-Jeong KIM
- Research Scientist
- Ayako KOHYAMA
- Research Scientist
- Yasuko NAGATSUKA
- Research Scientist
- yohei ISHIBASHI
- Special Postdoctoral Researcher
- Kayoko ESAKI
- Junior Research Associate
- Eriko OSHIMA
- Technical Staff I
- Chika SHIMIZU
- Technical Staff I
- Yoshimi ASANO
- Technical Staff II
- Kiyoko SHIMAZAKI
- Technical Staff II
- Keiko KATO
- Visiting Scientist
- Shun WATANABE
- Visiting Scientist
- Shigeki FURUYA
- Visiting Scientist
- Hideyoshi HIGASHI
- Visiting Scientist
- Sumiko HAMANAKA
- Visiting Scientist
- Takamitsu SANO
- Visiting Scientist
- Yoko OHASHI
- Research Collaborative Advisor
- Kumi ISHII
- Part-time Staff
- Tomoko SHIMIZU
- Part-time Staff
- Kiyoka AMADA
- Part-time Staff