Postsynaptic shank antagonizes dendrite branching induced by the leucine-rich repeat protein Densin-180

J Neurosci. 2005 Jan 12;25(2):479-87. doi: 10.1523/JNEUROSCI.2699-04.2005.


Leucine-rich repeat and PDZ [postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1] domain proteins such as scribble and Densin-180 have been implicated in the establishment of cell-cell contacts. Here, we show that Densin-180, which has been identified as a constituent of the postsynaptic density in excitatory synapses interacts with the postsynaptic scaffold protein shank (shank1-3). The interaction involves a two-point attachment of the C-terminal region of Densin-180 with the Src homology 3 domain and the N-terminal part of the proline-rich region of shank proteins. The N-terminal leucine-rich repeat region, which is not involved in binding shank, targets Densin-180 to the plasma membrane in transfected cells and to the basolateral membrane of epithelial cells. Nevertheless, coexpression of shank leads to a redirection of Densin-180 into intracellular clusters. In cultured hippocampal neurons, Densin-180 overexpression induces excessive branching of neuronal dendrites, which occurs at the expense of clusters for the postsynaptic marker PSD-95. Coexpression of shank3 abrogates branch formation and targets Densin-180 into postsynaptic clusters instead. Shank blocks binding of delta-catenin but not alphaCaM kinase II to Densin-180; because delta-catenin has been shown to induce branching and neurite formation, our data suggest a mechanism where shank could block the activation of a Densin-180-dependent signaling pathway by delta-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Cells, Cultured
  • Dendrites / physiology*
  • Disks Large Homolog 4 Protein
  • Dogs
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Leucine-Rich Repeat Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Protein Binding
  • Protein Structure, Tertiary
  • Proteins / metabolism
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae
  • Sialoglycoproteins / chemistry
  • Sialoglycoproteins / metabolism
  • Sialoglycoproteins / physiology*
  • src Homology Domains


  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • LRRC7 protein, human
  • Leucine-Rich Repeat Proteins
  • Lrrc7 protein, rat
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Proteins
  • Recombinant Fusion Proteins
  • Sialoglycoproteins
  • postsynaptic density proteins