Identification of a neuronal endocytic pathway activated by an apolipoprotein E (apoE) receptor binding peptide
Identification of a neuronal endocytic pathway activated by an apolipoprotein E (apoE) receptor binding peptide
复制标题
DOI：
10.1016/s0006-8993(97)00877-9
复制
发表时间：
1997-12-05
期刊：
影响因子：
2.9
通讯作者：
Gruenstein, E
中科院分区：
文献类型：
--
作者：
Wang, WS;Ciraolo, G;Gruenstein, E
载脂蛋白E（apoE）是唯一也存在于脑血管外液中的血清载脂蛋白，在脑血管外液中，它被认为在中枢神经系统的脂质转运中起重要作用。此外，apoE还与神经再生过程和阿尔茨海默病的病因学有关。来源于apoE受体结合结构域的肽具有生物活性，并与低密度脂蛋白（LDL）受体和LDL受体相关蛋白结合。然而，没有直接证据表明这些apoE肽能够直接激活脑或其他地方的内吞过程。在本文中，我们已经使用电子显微镜和视频成像荧光显微镜研究了来自人apoE受体结合域的肽对培养的大鼠皮层神经元内吞作用的影响。我们已经发现，这种串联二聚体重复肽通过受体相关蛋白敏感途径诱导神经元内吞作用。虽然该肽诱导细胞质钙升高，但这不是诱导内吞作用所必需的。另一方面，内吞囊泡的正常加工似乎确实需要胞浆钙的升高。因为钙反应的抑制导致大的内吞囊泡的积累。(C)1997年Elsevier Science B.V.
Apolipoprotein E (apoE) is the only serum apolipoprotein that is also found in the extravascular fluid of the brain, where it is thought to play an important role in lipid transport in the central nervous system. In addition apoE has also been implicated in neural regenerative processes and in the etiology of Alzheimer's disease. Peptides derived from the receptor binding domain of apoE are biologically active and bind to low density lipoprotein (LDL) receptors and LDL receptor related protein. There is, how ever, no direct evidence that these apoE peptides are able to directly activate the endocytic process, either in the brain or elsewhere. In the present paper, we have used electron microscopy and video imaging fluorescence microscopy to investigate the effects of a peptide derived from the receptor binding domain of human apoE on endocytosis in cultured rat cortical neurons. We have found that this tandem dimer repeat peptide induces neuronal endocytosis via a receptor associated protein sensitive pathway. Although the peptide induces a rise in cytoplasmic calcium, this is not required for the induction of endocytosis. On the other hand, normal processing of the endocytic vesicles does appear to require the elevation of cytoplasmic calcium. since inhibition of the calcium response results in the accumulation of large endocytic vesicles. (C) 1997 Elsevier Science B.V.