Changes in the morphology of neuronal dendritic spines are correlated with changes in synaptic plasticity. The cell surface proteoglycan syndecan-2 is clustered at the surface of mature hippocampal neurons and is thought to regulate structural changes of the spines. Ethell et al. demonstrate that syndecan-2 is phosphorylated on at least two tyrosine residues by the receptor-type tyrosine kinase EphB2 in vitro and in vivo. The two transmembrane proteins colocalized in dendrites of hippocampal neurons and were isolated in a complex from mouse brain neurons. Phosphorylation was required for their interaction, for syndecan-2 to cluster, and for normal dendritic spine formation in transfected neurons. The authors propose that phosphorylation triggers clustering of syndecan-2, and that the EphB2-syndecan-2 complex subsequently initiates the recruitment of downstream signaling molecules that control dendritic spine formation. I.M. Ethell, F. Irie, M.S. Kalo, J.R. Couchman, E.B. Pasquale, Y. Yamaguchi, EphB/Syndecan-2 signaling in dendritic spine morphogenesis. Neuron 31 , 1001-1013 (2001). [Full Text]