Pyroglutamate-amyloid-β and glutaminyl cyclase are colocalized with amyloid-β in secretory vesicles and undergo activity-dependent, regulated secretion.
Pyroglutamate-amyloid-β and glutaminyl cyclase are colocalized with amyloid-β in secretory vesicles and undergo activity-dependent, regulated secretion.
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DOI：
10.1159/000358430
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Hook V
中科院分区：
文献类型：
--
作者：
Cynis H;Funkelstein L;Toneff T;Mosier C;Ziegler M;Koch B;Demuth HU;Hook V
N-截短的pGlu-Aβ（3-40/42）肽是促进Aβ肽积累的关键组分，导致阿尔茨海默病中的神经变性和记忆丧失。由于Aβ在脑中的沉积是以活性依赖性方式发生的，因此确定用于通过β-氨基环化酶产生pGlu-Aβ（3-40/42）的亚细胞器以及它们与全长Aβ（1-40/42）肽的定位以调节分泌是重要的。因此，本研究的目的是研究假设pGlu-Aβ和β-氨基环化酶（QC）与Aβ共定位在分泌囊泡（DCSV）中，与神经递质一起进行活性依赖性分泌。评估纯化的DCSV的pGlu-Aβ（3-40/42）、Aβ（1-40/42）、QC和神经递质。分析神经元样嗜铬细胞的pGlu-Aβ、QC、Aβ和神经肽的共分泌。用QC抑制剂处理细胞并测量pGlu-Aβ。还检查了人神经母细胞瘤细胞的pGlu-Aβ和QC。分离的DCSV含有pGlu-Aβ（3-40/42）、QC和Aβ（1-40/42），以及神经肽和儿茶酚胺类神经递质。细胞pGlu-Aβ（3-40/42）和QC与Aβ（1-40/42）、脑啡肽和甘丙肽神经递质进行活性依赖性共分泌。QC抑制剂可降低pGlu-Aβ水平。人神经母细胞瘤细胞显示与QC共定位的pGlu-Aβ的调节分泌。PyroGlu-Aβ和QC与Aβ一起存在于DCSV中，并与神经递质进行活性依赖性调节共分泌。
N-truncated pGlu-Aβ(3-40/42) peptides are key components that promote Aβ peptide accumulation, leading to neurodegeneration and memory loss in Alzheimer’s disease. Because Aβ deposition in brain occurs in an activity-dependent manner, it is important to define the subcellular organelle for pGlu-Aβ(3-40/42) production by glutaminyl cyclase, and their localization with full-length Aβ(1-40/42) peptides for regulated secretion. Therefore, the objective of this study was to investigate the hypothesis that pGlu-Aβ and glutaminyl cyclase (QC) are co-localized with Aβ in secretory vesicles (DCSV) for activity-dependent secretion with neurotransmitters. Purified DCSV was assessed for pGlu-Aβ(3-40/42), Aβ(1-40/42), QC, and neurotransmitters. Neuronal-like chromaffin cells were analyzed for co-secretion of pGlu-Aβ, QC, Aβ, and neuropeptides. Cells were treated with a QC inhibitor and pGlu-Aβ was measured. Human neuroblastoma cells were also examined for pGlu-Aβ and QC. Isolated DCSV contain pGlu-Aβ(3-40/42), QC, and Aβ(1-40/42) with neuropeptide and catecholamine neurotransmitters. Cellular pGlu-Aβ(3-40/42) and QC undergo activity-dependent co-secretion with Aβ(1-40/42) and enkephalin and galanin neurotransmitters. A QC inhibitor decreased levels of pGlu-Aβ. Human neuroblastoma cells displayed regulated secretion of pGlu-Aβ that is co-localized with QC. PyroGlu-Aβ and QC are present with Aβ in DCSV, and undergo activity-dependent, regulated co-secretion with neurotransmitters.
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DOI：
10.1006/bbrc.2000.3490
发表时间：
2000-09-24
影响因子：
3.1
作者：
Harigaya, Y;Saido, TC;Younkin, SG
通讯作者：
Younkin, SG
影响因子：
2.9
作者：
Fraering, PC;Ye, WJ;Wolfe, MS
通讯作者：
Wolfe, MS
影响因子：
64.5
作者：
Huang Y;Mucke L
通讯作者：
Mucke L
影响因子：
4.8
作者：
Hwang, Shin-Rong;Garza, Christina;Hook, Vivian
通讯作者：
Hook, Vivian
影响因子：
3.7
作者：
Bark SJ;Wegrzyn J;Taupenot L;Ziegler M;O'Connor DT;Ma Q;Smoot M;Ideker T;Hook V
通讯作者：
Hook V