Gamma-protocadherin homophilic interaction and intracellular trafficking is controlled by the cytoplasmic domain in neurons
Molecular and Cellular Neuroscience. 2009-03-01; 40(3): 344-353
DOI: 10.1016/j.mcn.2008.12.002
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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.