Synbindin, A novel syndecan-2-binding protein in neuronal dendritic spines.
Dendritic spines are small protrusions on the surface of dendrites that receive the vast majority of excitatory synapses. We previously showed that the cell-surface heparan sulfate proteoglycan syndecan-2 induces spine formation upon transfection into hippocampal neurons. This effect requires the COOH-terminal EFYA sequence of syndecan-2, suggesting that cytoplasmic molecules interacting with this sequence play a critical role in spine morphogenesis. Here, we report a novel protein that binds to the EFYA motif of syndecan-2. This protein, named synbindin, is expressed by neurons in a pattern similar to that of syndecan-2, and colocalizes with syndecan-2 in the spines of cultured hippocampal neurons. In transfected hippocampal neurons, synbindin undergoes syndecan-2-dependent clustering. Synbindin is structurally related to yeast proteins known to be involved in vesicle transport. Immunoelectron microscopy localized synbindin on postsynaptic membranes and intracellular vesicles within dendrites, suggesting a role in postsynaptic membrane trafficking. Synbindin coimmunoprecipitates with syndecan-2 from synaptic membrane fractions. Our results show that synbindin is a physiological syndecan-2 ligand on dendritic spines. We suggest that syndecan-2 induces spine formation by recruiting intracellular vesicles toward postsynaptic sites through the interaction with synbindin.
Ethell
I M
IM
The Burnham Institute, La Jolla, California 92037, USA.
Hagihara
K
K
Miura
Y
Y
Irie
F
F
Yamaguchi
Y
Y
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D003712:Dendrites / Q000737:chemistry* / Q000648:ultrastructure; D015723:Gene Library; D006624:Hippocampus / Q000166:cytology; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry* / Q000648:ultrastructure; D015388:Organelles / Q000737:chemistry / Q000648:ultrastructure; D011485:Protein Binding; D011509:Proteoglycans / Q000302:isolation & purification / Q000378:metabolism*; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D017386:Sequence Homology, Amino Acid; D053669:Syndecan-2; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; C508246:Sdc2 protein, mouse; C508247:Sdc2 protein, rat; C415482:Trappc4 protein, mouse; D033921:Vesicular Transport Proteins; D053669:Syndecan-2