Expression and alternate splicing of apolipoprotein E receptor 2 in brain
Expression and alternate splicing of apolipoprotein E receptor 2 in brain
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DOI：
10.1016/s0306-4522(98)00489-8
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发表时间：
1999-01-01
期刊：
影响因子：
3.3
通讯作者：
Rebeck, GW
中科院分区：
文献类型：
--
作者：
Clatworthy, AE;Stockinger, W;Rebeck, GW
载脂蛋白E亚型影响阿尔茨海默病的发病风险。载脂蛋白E相关的风险可能与其结合和清除细胞表面受体，包括低密度脂蛋白受体家族的成员。我们研究了这个受体家族的最新成员载脂蛋白E受体2在人脑和胎盘中的表达。我们分析载脂蛋白E受体2信使RNA的逆转录-聚合酶链反应和载脂蛋白E受体2蛋白的免疫组化。在胎儿和成人脑组织中，载脂蛋白E受体2的四个外显子信息被交替剪接。外显子5，编码的7个配体结合重复序列中的3个，载脂蛋白E受体2的信使RNA检查中不存在。缺乏编码表皮生长因子前体重复序列的第8号外显子、编码O-糖基化区域的第15号外显子或编码胞质结构域的第18号外显子的载脂蛋白E受体2信息也作为微小剪接变体存在于大脑和胎盘中。在对照组和阿尔茨海默病组大脑中，载脂蛋白E受体2剪接模式没有观察到差异。免疫组化结果显示，载脂蛋白E受体2在小鼠全脑神经元均有表达，其中在海马锥体神经元、齿状回颗粒细胞、皮质神经元和小脑浦肯野细胞中表达最强，是第四种在神经元细胞上发现的载脂蛋白E受体。(C)1999年IBRO。出版社：Elsevier Science Ltd
Apolipoprotein E isoforms affect the risk of developing Alzheimer's disease. Apolipoprotein E-associated risk may be related to its binding to and clearance by cell surface receptors, including members of the low-density lipoprotein receptor family. We examined the brain expression of the most recently identified member of this receptor family, apolipoprotein E receptor 2, in human brain and placenta. We analysed apolipoprotein E receptor 2 messenger RNA by reverse transcription-polymerase chain reaction and apolipoprotein E receptor 2 protein by immunohistochemistry. Four exons of the apolipoprotein E receptor 2 message were alternately spliced in both fetal and adult brain tissue. Exon 5, encoding three of the seven ligand binding repeats, was absent in the apolipoprotein E receptor 2 messenger RNA examined. Apolipoprotein E receptor 2 messages lacking exon 8, encoding an epidermal growth factor precursor repeat, exon 15, encoding the O-glycosylation region, or exon 18, encoding a cytoplasmic domain, were also present as minor splice variants in the brain and placenta. No differences were observed in the pattern of apolipoprotein E receptor 2 splicing between control and Alzheimer brains. Immunohistochemistry of mouse brain showed that apolipoprotein E receptor 2 was expressed in neurons throughout the brain, with strong expression in pyramidal neurons of the hippocampus, granule cells of the dentate gyrus, cortical neurons and Purkinje cells of the cerebellum.Thus, apolipoprotein E receptor 2 is the fourth apolipoprotein E receptor identified on neuronal cells. (C) 1999 IBRO. Published by Elsevier Science Ltd.