Activation of ephrin-B1 (EFNB1) and ephrin-B2 (EFNB2) by postsynaptic EPHB receptors initiates presynaptic differentiation and causes increases in the density of presynaptic release sites. The EPHB-EFNB interaction recruits the adaptor protein syntenin-1 (SDCBP) through the PDZ-binding domain of EFNBs. SDCBP colocalizes with EFNB1 and EFNB2 at synaptic contacts and knockdown of EFNBs leads to a reduction in the number of synaptic contacts. SDCBP provides a direct link by which EFNB can associate with a protein complex involved in the recruitment and regulation of presynaptic vesicles. McClelland et al. suggest a model whereby SDCBP recruits multidomain scaffolding molecules that enables the clustering of synaptic vesicles including ERC2/CAST1, RIM1 and Rab synaptic vesicle proteins (McClelland et al. 2009).