title: Gamma-protocadherin homophilic interaction and intracellular trafficking is controlled by the cytoplasmic domain in neurons.
abstract: 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.
authors.affiliation: Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Fernández-Monreal
authors.forename: Semie
authors.initials: S
authors.lastname: Kang
authors.forename: Greg R
authors.initials: GR
authors.lastname: Phillips
mesh_terms: D000818:Animals; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D015388:Organelles / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
chemical_list: D000070585:Cadherin Related Proteins; D015820:Cadherins; C464785:Gamma-protocadherins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins