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首页> 外文期刊>The European Journal of Neuroscience >Gamma-protocadherins are enriched and transported in specialized vesicles associated with the secretory pathway in neurons.
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Gamma-protocadherins are enriched and transported in specialized vesicles associated with the secretory pathway in neurons.

机译：γ-procadcadherins在与神经元分泌途径相关的特殊囊泡中富集和运输。

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摘要

Gamma protocadherins (Pcdh-gammas) 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-gamma 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-gammas 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-gamma-containing organelles in synaptic compartments was observed at postnatal day 16. To determine the origin of Pcdh-gamma-trafficking organelles, we isolated organelles with Pcdh-gamma 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-gamma antibody but not with the classical cadherin antibody. In cultured hippocampal neurons, Pcdh-gamma immunolabeling partially overlapped with calnexin- and COPII-positive puncta in dendrites. Mobile Pcdh-gamma-GFP profiles dynamically codistributed with a DsRed construct coupled to ER retention signals by live imaging. Pcdh-gamma expression correlated with accumulations of tubulovesicular and ER-like organelles in dendrites. Our results are consistent with the possibility that Pcdh-gammas could have a unique function within the secretory pathway in addition to their documented surface roles.
机译：γ原钙粘蛋白（Pcdh-gammas）与经典钙粘蛋白相似，具有参与具有同源特性的细胞间相互作用的潜力。越来越多的证据表明某些原钙粘蛋白在神经发育中具有非常规作用。我们试图确定神经元中的Pcdh-γ转运是否与这些分子的细胞内作用一致。在这里，我们显示，与经典钙粘蛋白的大部分表面定位相反，内源性Pcdh-gammas主要在体内大鼠神经元内，并且平均分布在突触下树突状和轴突区室的细胞器中。在出生后第16天观察到突触隔室中含Pcdh-γ的细胞器比例高得多。为了确定Pcdh-γ贩运细胞器的起源，我们从脑细胞器悬液中分离了带有Pcdh-γ抗体偶联磁珠的细胞器。具有高水平COPII和内质网-高尔基体中间区（ERGIC）成分的囊泡是用Pcdh-γ抗体而不是经典钙粘蛋白抗体分离的。在培养的海马神经元中，Pcdh-γ免疫标记在树突中与钙联接蛋白和COPII阳性小点部分重叠。移动Pcdh-gamma-GFP配置文件与通过实时成像与ER保留信号偶联的DsRed结构动态共分布。 Pcdh-γ表达与树突状微管和ER样细胞器的积累有关。我们的研究结果与Pcdh-gammas除了已记录的表面作用外，在分泌途径中可能具有独特功能的可能性是一致的。

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