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

J Cell Biol. 2000 Oct 2;151(1):53-68. doi: 10.1083/jcb.151.1.53.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Biological Transport
  • Carrier Proteins / genetics
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • Dendrites / chemistry*
  • Dendrites / ultrastructure
  • Gene Library
  • Hippocampus / cytology
  • Membrane Glycoproteins / isolation & purification
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / isolation & purification
  • Nerve Tissue Proteins / metabolism*
  • Neurons / chemistry*
  • Neurons / ultrastructure
  • Organelles / chemistry
  • Organelles / ultrastructure
  • Protein Binding
  • Proteoglycans / isolation & purification
  • Proteoglycans / metabolism*
  • RNA, Messenger / isolation & purification
  • Rats
  • Sequence Homology, Amino Acid
  • Syndecan-2
  • Tissue Distribution
  • Two-Hybrid System Techniques
  • Vesicular Transport Proteins*

Substances

  • Carrier Proteins
  • DNA, Complementary
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Proteoglycans
  • RNA, Messenger
  • Sdc2 protein, mouse
  • Sdc2 protein, rat
  • Trappc4 protein, mouse
  • Vesicular Transport Proteins
  • Syndecan-2

Associated data

  • GENBANK/AF233340