EphB/syndecan-2 signaling in dendritic spine morphogenesis

We previously reported that the cell surface proteoglycan syndecan-2 can in duce dendritic spine formation in hippocampal neurons. We demonstrate here that the EphB2 receptor tyrosine kinase phosphorylates syndecan-2 and that this phosphorylation event is crucial for syndecan-2 clustering and spine f ormation. Syndecan-2 is tyrosine phosphorylated and forms a complex with Ep hB2 in mouse brain. Dominant-negative inhibition of endogenous EphB recepto r activities blocks clustering of endogenous syndecan-2 and normal spine fo rmation in cultured hippocampal neurons. This is the first evidence that Ep h receptors play a physiological role in dendritic spine morphogenesis. Our observations suggest that spine morphogenesis is triggered by the activati on of Eph receptors, which causes tyrosine phosphorylation of target molecu les, such as syndecan-2, in presumptive spines.