title: γ-protocadherins are enriched and transported in specialized vesicles associated with the secretory pathway in neurons.
abstract: Gamma protocadherins (Pcdh-γs) resemble classical cadherins and have the potential to engage in cell-cell interactions with homophilic properties. Emerging evidence suggests non-conventional roles for some protocadherins in neural development. We sought to determine whether Pcdh-γ trafficking in neurons is consistent with an intracellular role for these molecules. Here we show that, in contrast to the largely surface localization of classical cadherins, endogenous Pcdh-γs are primarily intracellular in rat neurons in vivo and are equally distributed within organelles of subsynaptic dendritic and axonal compartments. A strikingly higher proportion of Pcdh-γ-containing organelles in synaptic compartments was observed at postnatal day 16. To determine the origin of Pcdh-γ-trafficking organelles, we isolated organelles with Pcdh-γ antibody-coupled magnetic beads from brain organelle suspensions. Vesicles with high levels of COPII and endoplasmic reticulum-Golgi intermediate compartment (ERGIC) components were isolated with the Pcdh-γ antibody but not with the classical cadherin antibody. In cultured hippocampal neurons, Pcdh-γ immunolabeling partially overlapped with calnexin- and COPII-positive puncta in dendrites. Mobile Pcdh-γ-GFP profiles dynamically codistributed with a DsRed construct coupled to ER retention signals by live imaging. Pcdh-γ expression correlated with accumulations of tubulovesicular and ER-like organelles in dendrites. Our results are consistent with the possibility that Pcdh-γs could have a unique function within the secretory pathway in addition to their documented surface roles.
authors.affiliation: Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Mónica
authors.initials: M
authors.lastname: Fernández-Monreal
authors.forename: Twethida
authors.initials: T
authors.lastname: Oung
authors.forename: Hugo H
authors.initials: HH
authors.lastname: Hanson
authors.forename: Robert
authors.initials: R
authors.lastname: O'Leary
authors.forename: William G
authors.initials: WG
authors.lastname: Janssen
authors.forename: Georgia
authors.initials: G
authors.lastname: Dolios
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Greg R
authors.initials: GR
authors.lastname: Phillips
mesh_terms: D000818:Animals; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000378:metabolism*; D002478:Cells, Cultured; D009474:Neurons / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055571:Secretory Pathway / Q000502:physiology*; D022142:Secretory Vesicles / Q000378:metabolism* / Q000502:physiology
chemical_list: D000070585:Cadherin Related Proteins; D015820:Cadherins; C464785:Gamma-protocadherins