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Takashi Amanuma, Soh Osuka, Eriko Osima, Ryo Taguchi, Yoshio Hirabayashi, Miwako Ozaki(2008). Neuregulin Receptors, ErbB Are Localized in Microdomain Lipid Raft of Cerebellar Granule Cells with Different Neural Activitie. J. of SJWS 9: 51-58
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Neuregulin Receptors, ErbB Are Localized in Microdomain Lipid Raft
of Cerebellar Granule Cells with Different Neural Activities
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Takashi Amanumaa,b, Soh Osukac, Eriko Osimac, Ryo Taguchid, Yoshio Hirabayashic,
Miwako Ozaki*a, e, f
a Laboratory of Neural Disorders, WOBRI (Waseda-Olympus Bioscience Research Institute), Helios, #05-01/02, 11 Biopolis Way, 138667 Singapore, bResearch Center of Brain and Oral Science, Craniofacial Growth and Development Dentistry, Kanagawa Dental College, Japan, cHirabayashi Research Unit, Brain Science Institute, RIKEN (The Institute of Physical and Chemical Research), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan, dDepartment of Metabolome, Advanced Research Center for Biological Science, The University of Tokyo, Japan, eInstitute for Biomedical Engineering, Consolidated Research Institute for Advanced Science and Medical Care (ASMeW), fComprehensive Research Organization, Waseda University, Rm. 127, Bldg. 120-5, 513 Waseda Tsurumaki-cho, Shinjuku-ku, Tokyo, 162-0041 Japan
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Abstract: ErbB receptors, a kind of subfamily of receptor-type tyrosine kinase, are receptors for epidermal growth factor (EGF) and neuregulin (NRG) a neurotrophic factor, which play multifunctional roles in the development of nervous systems and the acquisition of higher-order functions. The ErbB/NRG signaling regulates the activity of ion channels and neurotransmitter receptors in synapses, and its dysfunction causes neurodegenerative and mental disorders (particularly schizophrenia). To know the regulation mechanism of ErbB signaling on participation of membrane composition, we examined the role of microdomains glipid raftsh in primary cultured neurons. We separated the lipid raft membrane fractions, and examined lipid and protein compositions under the condition of low (5mM) and high (30mM) KCl concentrations in cerebellar granule cells. The dynamics of lipid composition and synaptic proteins changed according to concentrations of KCl. In high KCl treatment, phosphatidylcholine (PC) with saturated fatty acids was characteristically increased and PC species containing polyunsaturated fatty acids was decreased. ErbB2, B4 proteins were shifted to the raft fractions. Low KCl and depletion of cholesterol/sphingolipid led to loss of synapse-like structure. The remaining punctuated signals became greatly enlarged. As other proteins, NMDAR, NR1 and PSD95/93 protein distribution changed by different KCl concentrations. Our findings demonstrate a critical role for lipid rafts in NRG signaling and modulation of synaptic plasticity in the central nervous system.
Keywords: ErbB-NRG signaling, primary cultured neurons, lipid raft, activity-dependent, schizophrenia.
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