Gamma-protocadherin Homophilic Interaction and Intracellular Trafficking Is Controlled by the Cytoplasmic Domain in Neurons

Mol Cell Neurosci. 2009 Mar;40(3):344-53. doi: 10.1016/j.mcn.2008.12.002. Epub 2008 Dec 16.


Gamma-protocadherins (Pcdh-gammas) are good candidates to mediate specificity in synaptogenesis but their role in cell-cell interactions is a matter of debate. We proposed that Pcdh-gammas modify preformed synapses via trafficking of Pcdh-gammas-containing organelles, insertion into synaptic membranes and homophilic transcellular interaction. Here we provide evidence in support of this model. We show for the first time that Pcdh-gammas have homophilic properties and that they accumulate at dendro-dendritic and axo-dendritic interfaces during neuronal development. Pcdh-gammas are maintained in a substantial mobile intracellular pool in dendrites and cytoplasmic deletion shifts the molecule to the surface and reduces the number and velocity of the mobile packets. We monitored Pcdh-gamma temporal and spatial dynamics in transport organelles. Pcdh-gamma organelles bud and fuse with stationary clusters near synapses. These results suggest that Pcdh-gamma-mediated cell-cell interactions in synapse development or maintenance are tightly regulated by control of intracellular trafficking via the cytoplasmic domain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / chemistry
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Differentiation / physiology
  • Cell Line
  • Humans
  • Intercellular Junctions / physiology
  • Mice
  • Neurons / cytology
  • Neurons / physiology*
  • Organelles / metabolism
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Protein Structure, Tertiary
  • Protein Transport / physiology
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Synapses / metabolism


  • Cadherins
  • Gamma-protocadherins
  • Protein Isoforms
  • Recombinant Fusion Proteins