Nencki Institute of Experimental Biology, Warsaw, Poland.
Max-Delbrueck Center for Molecular Medicine, Berlin, Germany; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Trends Neurosci. 2020 Nov;43(11):870-885. doi: 10.1016/j.tins.2020.08.003. Epub 2020 Sep 4.
VPS10P (vacuolar protein sorting 10 protein) domain receptors are neuronal sorting receptors that direct cargo proteins to their destined location in subcellular compartments of the soma, dendrites, and the axon. Protein sorting by receptors such as SORLA, sortilin, and SorCS2 controls functional integrity and viability of neurons, whereas sorting receptor dysfunctions are linked to acute, psychiatric, and neurodegenerative diseases. Here, we discuss molecular mechanisms that define ligand repertoire and sorting path and that control plasticity of VPS10P domain receptor expression in the healthy brain and in response to injury. These findings highlight important concepts in neuronal protein sorting and why aberrant sorting contributes to the progression of devastating diseases of the human brain, including epilepsy, Alzheimer's disease, and frontotemporal dementia.
VPS10P（液泡蛋白分选 10 蛋白）结构域受体是神经元分拣受体，可将货物蛋白导向其在神经元胞体、树突和轴突的亚细胞隔室中的预定位置。SORLA、sortilin 和 SorCS2 等受体的蛋白分拣控制着神经元的功能完整性和存活能力，而分拣受体功能障碍与急性、精神疾病和神经退行性疾病有关。在这里，我们讨论了定义配体谱和分拣途径的分子机制，并控制了 VPS10P 结构域受体在健康大脑中的表达和对损伤的反应的可塑性。这些发现强调了神经元蛋白分拣的重要概念，以及为什么异常分拣会导致人类大脑毁灭性疾病的进展，包括癫痫、阿尔茨海默病和额颞叶痴呆。
