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 “lipid rafts” 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.
