1529-240127282007Jul11J NeurosciPostsynaptic ephrinB3 promotes shaft glutamatergic synapse formation.750875197508-19Excitatory synapses in the CNS are formed on both dendritic spines and shafts. Recent studies show that the density of shaft synapses may be independently regulated by behavioral learning and the induction of synaptic plasticity, suggesting that distinct mechanisms are involved in regulating these two types of synapses. Although the molecular mechanisms underlying spinogenesis and spine synapse formation are being delineated, those regulating shaft synapses are still unknown. Here, we show that postsynaptic ephrinB3 expression promotes the formation of glutamatergic synapses specifically on the shafts, not on spines. Reducing or increasing postsynaptic ephrinB3 expression selectively decreases or increases shaft synapse density, respectively. In the ephrinB3 knock-out mouse, although spine synapses are normal, shaft synapse formation is reduced in the hippocampus. Overexpression of glutamate receptor-interacting protein 1 (GRIP1) rescues ephrinB3 knockdown phenotype by restoring shaft synapse density. GRIP1 knockdown prevents the increase in shaft synapse density induced by ephrinB3 overexpression. Together, our results reveal a novel mechanism for independent modulation of shaft synapses through ephrinB3 reverse signaling.AotoJasonJDepartment of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA.TingPamelaPMaghsoodiBitaBXuNanjieNHenkemeyerMarkMChenLuLengR01 MH066332MHNIMH NIH HHSUnited StatesR01 MH069792MHNIMH NIH HHSUnited StatesMH069792MHNIMH NIH HHSUnited StatesMH66332MHNIMH NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't