Gamma-protocadherins are enriched and transported in specialized vesicles associated with the secretory pathway in neurons

Mónica Fernández-Monreal, Twethida Oung, Hugo H. Hanson, Robert O'Leary, William G. Janssen, Georgia Dolios, Rong Wang, Greg R. Phillips

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish
Pages (from-to)921-931
Number of pages11
JournalEuropean Journal of Neuroscience
Volume32
Issue number6
DOIs
StatePublished - Sep 2010

Keywords

  • adhesion
  • dendrite
  • live-cell imaging
  • organelle
  • protocadherin

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