The related neuronal endosomal proteins NEEP21 (Nsg1) and P19 (Nsg2) have divergent expression profiles in vivo.
The related neuronal endosomal proteins NEEP21 (Nsg1) and P19 (Nsg2) have divergent expression profiles in vivo.
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DOI：
10.1002/cne.24168
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发表时间：
2017-06-01
期刊：
影响因子：
--
通讯作者：
Winckler B
中科院分区：
文献类型：
--
作者：
Barford K;Yap CC;Dwyer ND;Winckler B
内体成熟和运输构成了存在于所有细胞类型中的复杂运输系统。神经元已经调整了它们的内体系统以满足它们独特而复杂的需求。这些适应包括重新利用现有的蛋白质以使内吞作用和运输多样化，以及某些调节因子在神经元中的优先表达高于其他细胞类型。这些神经元调节因子包括神经元特异性基因家族成员（Nsg）、NEEP 21（Nsg 1）和P19（Nsg 2）。NEEP 21/Nsg 1在细胞粘附分子L1/NgCAM、神经递质受体GluA 2和β-APP等多种受体的运输中发挥作用。然而，目前尚不清楚NEEP 21/Nsg 1和P19/Nsg 2在体内何时何地表达，以及这两种蛋白是否总是共表达。在这里，我们表明，NEEP 21/Nsg 1和P19/Nsg 2存在于重叠和不同的细胞群在海马，新皮层，小脑发育过程中。NEEP 21/Nsg 1和P19/Nsg 2在胚胎发育期间水平最高，并且在幼年小鼠脑中持续表达。特别是，一个子集的第V层皮层神经元保持相对较高的表达NEEP 21/Nsg 1和P19/Nsg 2在出生后第16天，以及在海马CA 1 -3区。在小脑中，NEEP 21/Nsg 1的表达在很大程度上局限于成年后的浦肯野神经元，而P19/Nsg 2的表达随着年龄的增长而明显消失。这种分歧和限制的表达可能反映了不同的神经元在不同的成熟阶段对这类运输调节剂的不同需求。
Endosomal maturation and transport constitutes a complex trafficking system present in all cell types. Neurons have adapted their endosomal system to meet their unique and complex needs. These adaptations include repurposing existing proteins to diversify endocytosis and trafficking, as well as preferential expression of certain regulators more highly in neurons than other cell types. These neuronal regulators include the family of Neuron-Specific Gene family members (Nsg), NEEP21 (Nsg1), and P19 (Nsg2). NEEP21/Nsg1 plays a role in the trafficking of multiple receptors, including the cell adhesion molecule L1/NgCAM, the neurotransmitter receptor GluA2, and β-APP. Recently, we showed that NEEP2/Nsg1 and P19/Nsg2 are not expressed in all neuronal cell types in vitro. However, it is not known where and when NEEP21/Nsg1 and P19/Nsg2 are expressed in vivo, and whether both proteins are always coexpressed. Here, we show that NEEP21/Nsg1 and P19/Nsg2 are present in both overlapping and distinct cell populations in the hippocampus, neocortex, and cerebellum during development. NEEP21/Nsg1 and P19/Nsg2 levels are highest during embryonic development, and expression persists in the juvenile mouse brain. In particular, a subset of layer V cortical neurons retains relatively high expression of both NEEP21/Nsg1 and P19/Nsg2 at postnatal day 16 as well as in the CA1-3 regions of the hippocampus. In the cerebellum, NEEP21/Nsg1 expression becomes largely restricted to Purkinje neurons in adulthood whereas P19/Nsg2 expression strikingly disappears from the cerebellum with age. This divergent and restricted expression likely reflects differential needs for this class of trafficking regulators in different neurons during different stages of maturation.
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