Present address: Centro De Biología Molecular Severo Ochoa, Nicolás Cabrera 1, Universidad Autónoma de Madrid, 28049-Madrid, Spain.
Gamma-protocadherins are enriched and transported in specialized vesicles associated with the secretory pathway in neurons
Article first published online: 3 SEP 2010
© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 32, Issue 6, pages 921–931, September 2010
How to Cite
Fernández-Monreal, M., Oung, T., Hanson, H. H., O’Leary, R., Janssen, W. G., Dolios, G., Wang, R. and Phillips, G. R. (2010), Gamma-protocadherins are enriched and transported in specialized vesicles associated with the secretory pathway in neurons. European Journal of Neuroscience, 32: 921–931. doi: 10.1111/j.1460-9568.2010.07386.x
- Issue published online: 17 SEP 2010
- Article first published online: 3 SEP 2010
- Received 4 February 2010, revised 21 June 2010, accepted 23 June 2010
- live-cell imaging;
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.