Gamma-protocadherins are enriched and transported in specialized vesicles associated with the secretory pathway in neurons
European Journal of Neuroscience. 2010-09-03; 32(6): 921-931
DOI: 10.1111/j.1460-9568.2010.07386.x
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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.
© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of
European Neuroscience Societies and Blackwell Publishing Ltd.