Amyloid-β precursor protein: Multiple fragments, numerous transport routes and mechanisms.
Amyloid-β precursor protein: Multiple fragments, numerous transport routes and mechanisms.
复制标题
DOI：
10.1016/j.yexcr.2014.12.014
复制
发表时间：
2015-05-15
影响因子：
3.7
通讯作者：
Muresan, Zoia Ladescu
中科院分区：
文献类型：
--
作者：
Muresan, Virgil;Muresan, Zoia Ladescu
关键词：
本文综述了淀粉样蛋白-β前体蛋白（APP）的神经元内转运，APP是一种广泛的后变性修饰和蛋白水解切割的跨膜蛋白。揭示APP转运的复杂性被证明是细胞生物学研究的一项具有挑战性的奋进，值得优先考虑，因为APP是阿尔茨海默病致病过程的核心。APP在神经元索马的内质网中合成后，沿沿着分泌、内吞和再循环途径进入细胞内转运。沿着这些途径，APP被切割成确定的片段集，这些片段本身被运输--大多数是独立的--到神经元中的不同位点，在那里它们发挥它们的功能。我们回顾了目前已知的路线和机制的全长APP的运输，APP片段，评论主要是研究运输广泛切割的蛋白质所带来的实验挑战。综述强调蛋白水解和翻译后修饰，细胞内运输，APP物种的功能之间的相互关系。今后仍需解决的一个目标是将关于APP运输的各种观点纳入一个连贯的画面。在这篇综述中，疾病的背景下，只有轻微的处理，重点是在正常条件下的APP运输的基本生物学。如图所示，APP运输的研究揭示了许多运输机制，其中一些是传统的，另一些是新的，有待探索。
This review provides insight into the intraneuronal transport of the Amyloid-β Precursor Protein (APP), the prototype of an extensively posttranslationally modified and proteolytically cleaved transmembrane protein. Uncovering the intricacies of APP transport proves to be a challenging endeavor of cell biology research, deserving increased priority, since APP is at the core of the pathogenic process in Alzheimer’s disease. After being synthesized in the endoplasmic reticulum in the neuronal soma, APP enters the intracellular transport along the secretory, endocytic, and recycling routes. Along these routes, APP undergoes cleavage into defined sets of fragments, which themselves are transported – mostly independently – to distinct sites in neurons, where they exert their functions. We review the currently known routes and mechanisms of transport of full-length APP, and of APP fragments, commenting largely on the experimental challenges posed by studying transport of extensively cleaved proteins. The review emphasizes the interrelationships between the proteolytic and posttranslational modifications, the intracellular transport, and the functions of the APP species. A goal remaining to be addressed in the future is the incorporation of the various views on APP transport into a coherent picture. In this review, the disease context is only marginally addressed; the focus is on the basic biology of APP transport in normal conditions. As shown, the studies of APP transport uncovered numerous mechanisms of transport, some of them conventional, and others, novel, awaiting exploration.
登录
查看更多内容
DOI：
10.1083/jcb.200301115
发表时间：
2003-10-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lee MS;Kao SC;Lemere CA;Xia W;Tseng HC;Zhou Y;Neve R;Ahlijanian MK;Tsai LH
通讯作者：
Tsai LH
影响因子：
11.4
作者：
Area-Gomez, Estela;Castillo, Maria Del Carmen Lara;Tambini, Marc D.;Guardia-Laguarta, Cristina;de Groof, Ad J. C.;Madra, Moneek;Ikenouchi, Junichi;Umeda, Masato;Bird, Thomas D.;Sturley, Stephen L.;Schon, Eric A.
通讯作者：
Schon, Eric A.
影响因子：
21.3
作者：
Guillaud, Laurent;Wong, Richard;Hirokawa, Nobutaka
通讯作者：
Hirokawa, Nobutaka
影响因子：
56.9
作者：
Cao, XW;Südhof, TC
通讯作者：
Südhof, TC
影响因子：
82.9
作者：
Hartmann, T;Bieger, SC;Beyreuther, K
通讯作者：
Beyreuther, K