Barford Kelly, Yap Chan Choo, Dwyer Noelle D, Winckler Bettina
Department of Cell Biology, University of Virginia, Charlottesville, Virginia.
J Comp Neurol. 2017 Jun 1;525(8):1861-1878. doi: 10.1002/cne.24168. Epub 2017 Mar 15.
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.
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。神经元已经使其内体系统适应以满足其独特而复杂的需求。这些适应包括重新利用现有蛋白质以实现内吞作用和运输的多样化，以及某些调节因子在神经元中的表达比其他细胞类型更高。这些神经元调节因子包括神经元特异性基因家族成员（Nsg）家族、NEEP21（Nsg1）和P19（Nsg2）。NEEP21/Nsg1在多种受体的运输中发挥作用，包括细胞粘附分子L1/NgCAM、神经递质受体GluA2和β-淀粉样前体蛋白（β-APP）。最近，我们发现NEEP2/Nsg1和P19/Nsg2在体外并非在所有神经元细胞类型中都有表达。然而，尚不清楚NEEP21/Nsg1和P19/Nsg2在体内何处以及何时表达，以及这两种蛋白质是否总是共表达。在这里，我们表明在发育过程中，NEEP21/Nsg1和P19/Nsg2存在于海马体、新皮层和小脑中重叠和不同的细胞群体中。NEEP21/Nsg1和P19/Nsg2的水平在胚胎发育期间最高，并且在幼年小鼠大脑中持续表达。特别是，V层皮质神经元的一个亚群在出生后第16天以及海马体的CA1-3区域中保留了相对较高水平的NEEP21/Nsg1和P19/Nsg2表达。在小脑中，NEEP21/Nsg1的表达在成年期主要局限于浦肯野神经元，而P19/Nsg2的表达随着年龄的增长在小脑中显著消失。这种不同且受限的表达可能反映了在成熟的不同阶段，不同神经元对这类运输调节因子的不同需求。
