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

ABSTRACT: Gamma protocadherins (Pcdh-?s) 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-? 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-?s 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-?-containing organelles in synaptic compartments was observed at postnatal day 16. To determine the origin of Pcdh-?-trafficking organelles, we isolated organelles with Pcdh-? 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-? antibody but not with the classical cadherin antibody. In cultured hippocampal neurons, Pcdh-? immunolabeling partially overlapped with calnexin- and COPII-positive puncta in dendrites. Mobile Pcdh-?-GFP profiles dynamically codistributed with a DsRed construct coupled to ER retention signals by live imaging. Pcdh-? expression correlated with accumulations of tubulovesicular and ER-like organelles in dendrites. Our results are consistent with the possibility that Pcdh-?s could have a unique function within the secretory pathway in addition to their documented surface roles.

SUBMITTER: Fernandez-Monreal M 

PROVIDER: S-EPMC3107561 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature