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低密度脂蛋白受体相关蛋白1在发育中和成熟的小鼠中枢神经系统的神经元和神经胶质细胞群体中存在差异表达。

Low Density Lipoprotein-Receptor Related Protein 1 Is Differentially Expressed by Neuronal and Glial Populations in the Developing and Mature Mouse Central Nervous System.

作者信息

Auderset Loic, Cullen Carlie L, Young Kaylene M

机构信息

Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, 7000, Australia.

出版信息

PLoS One. 2016 Jun 9;11(6):e0155878. doi: 10.1371/journal.pone.0155878. eCollection 2016.

Abstract

The low density lipoprotein-receptor related protein 1 (LRP1) is a large endocytic cell surface receptor that is known to interact with a variety of ligands, intracellular adaptor proteins and other cell surface receptors to regulate cellular behaviours ranging from proliferation to cell fate specification, migration, axon guidance, and lipid metabolism. A number of studies have demonstrated that LRP1 is expressed in the brain, yet it is unclear which central nervous system cell types express LRP1 during development and in adulthood. Herein we undertake a detailed study of LRP1 expression within the mouse brain and spinal cord, examining a number of developmental stages ranging from embryonic day 13.5 to postnatal day 60. We report that LRP1 expression in the brain peaks during postnatal development. On a cellular level, LRP1 is expressed by radial glia, neuroblasts, microglia, oligodendrocyte progenitor cells (OPCs), astrocytes and neurons, with the exception of parvalbumin+ interneurons in the cortex. Most cell populations exhibit stable expression of LRP1 throughout development; however, the proportion of OPCs that express LRP1 increases significantly from ~69% at E15.5 to ~99% in adulthood. We also report that LRP1 expression is rapidly lost as OPCs differentiate, and is absent from all oligodendrocytes, including newborn oligodendrocytes. While LRP1 function has been primarily examined in mature neurons, these expression data suggest it plays a more critical role in glial cell regulation-where expression levels are much higher.

摘要

低密度脂蛋白受体相关蛋白1(LRP1)是一种大型的内吞细胞表面受体,已知其能与多种配体、细胞内衔接蛋白及其他细胞表面受体相互作用,从而调节从增殖到细胞命运决定、迁移、轴突导向及脂质代谢等一系列细胞行为。多项研究表明LRP1在大脑中表达,但目前尚不清楚在发育过程及成年期,中枢神经系统的哪些细胞类型表达LRP1。在此,我们对小鼠脑和脊髓中LRP1的表达进行了详细研究,检测了从胚胎第13.5天到出生后第60天的多个发育阶段。我们报告称,脑内LRP1的表达在出生后发育阶段达到峰值。在细胞水平上,LRP1由放射状胶质细胞、神经母细胞、小胶质细胞、少突胶质前体细胞(OPC)、星形胶质细胞和神经元表达,但皮质中的小白蛋白阳性中间神经元除外。大多数细胞群体在整个发育过程中LRP1表达稳定;然而,表达LRP1的OPC比例从胚胎第15.5天的约69%显著增加到成年期的约99%。我们还报告称,随着OPC分化,LRP1表达迅速丧失,并且在所有少突胶质细胞中均不存在,包括新生少突胶质细胞。虽然LRP1的功能主要在成熟神经元中进行了研究,但这些表达数据表明它在胶质细胞调节中发挥着更关键的作用,而胶质细胞中的表达水平要高得多。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39cb/4900551/99583f7b40f5/pone.0155878.g001.jpg

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