Synbindin, a novel syndecan-2-binding protein in neuronal dendritic spines

Dendritic spines are small protrusions on the surface of dendrites that rec eive the vast majority of excitatory synapses. We previously showed that th e cell-surface heparan sulfate proteoglycan syndecan-2 induces spine format ion upon transfection into hippocampal neurons. This effect requires the CO OH-terminal EFYA sequence of syndecan-2, suggesting that cytoplasmic molecu les interacting with this sequence play a critical role in spine morphogene sis, Here, we report a novel protein that binds to the EFYA motif of syndec an-2. This protein, named synbindin, is expressed by neurons in a pattern s imilar to that of syndecan-2, and colocalizes with syndecan-2 in the spines of cultured hippocampal neurons. In transfected hippocampal neurons, synbi ndin undergoes syndecan-2-dependent clustering. Synbindin is structurally r elated to yeast proteins known to be involved in vesicle transport. Immunoe lectron microscopy localized synbindin on postsynaptic membranes and intrac ellular vesicles within dendrites, suggesting a role in postsynaptic membra ne trafficking. Synbindin coimmunoprecipitates with syndecan-2 from synapti c membrane fractions. Our results show that synbindin is a physiological sy ndecan-2 ligand on dendritic spines. We suggest that syndecan-2 induces spi ne formation by recruiting intracellular vesicles toward postsynaptic sites through the interaction with synbindin.