Sorting of the Alzheimer's disease amyloid precursor protein mediated by the AP-4 complex.
Sorting of the Alzheimer's disease amyloid precursor protein mediated by the AP-4 complex.
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DOI：
10.1016/j.devcel.2010.01.015
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发表时间：
2010-03-16
影响因子：
11.8
通讯作者：
Bonifacino, Juan S.
中科院分区：
文献类型：
--
作者：
Burgos, Patricia V.;Mardones, Gonzalo A.;Rojas, Adriana L.;daSilva, Luis L. P.;Prabhu, Yogikala;Hurley, James H.;Bonifacino, Juan S.
适配器蛋白4(AP-4)是最近发现的、特征最差的异四聚体适配器蛋白(AP)复合体家族的成员，它介导后高尔基体隔室跨膜货物的分选。在这里，我们报道了来自阿尔茨海默病淀粉样前体蛋白(APP)胞浆尾部的YKFFE序列与AP-4的μ4亚单位的相互作用。生化和X射线结晶学分析表明，APP序列的性质和μ4上结合位点的位置与其他信号-适配器相互作用不同。APP-AP-4相互作用的中断减少了APP对内小体的定位，并增强了γ分泌酶催化的APP对致病淀粉样蛋白-β多肽的切割。这些发现表明，APP和AP-4参与了一种不同类型的信号-适配器相互作用，该相互作用介导了APP从跨高尔基网络(TGN)到内小体的运输，从而减少了蛋白质的淀粉样蛋白加工。
Adaptor protein 4 (AP-4) is the most recently discovered and least well-characterized member of the family of heterotetrameric adaptor protein (AP) complexes that mediate sorting of transmembrane cargo in post-Golgi compartments. Herein we report the interaction of an YKFFE sequence from the cytosolic tail of the Alzheimer’s Disease amyloid precursor protein (APP) with the μ4 subunit of AP-4. Biochemical and X-ray crystallographic analyses reveal that the properties of the APP sequence and the location of the binding site on μ4 are distinct from those of other signal-adaptor interactions. Disruption of the APP-AP-4 interaction decreases localization of APP to endosomes and enhances γ-secretase-catalyzed cleavage of APP to the pathogenic amyloid-β peptide. These findings demonstrate that APP and AP-4 engage in a distinct type of signal-adaptor interaction that mediates transport of APP from the trans-Golgi network (TGN) to endosomes, thereby reducing amyloidogenic processing of the protein.
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影响因子：
3.3
作者：
Mardones, Gonzalo A.;Burgos, Patricia V.;Bonifacino, Juan S.
通讯作者：
Bonifacino, Juan S.
影响因子：
4.8
作者：
Ohno, H;Aguilar, RC;Bonifacino, JS
通讯作者：
Bonifacino, JS
DOI：
10.1073/pnas.89.6.2252
发表时间：
1992-03-15
影响因子：
11.1
作者：
CAPORASO, GL;GANDY, SE;GREENGARD, P
通讯作者：
GREENGARD, P
影响因子：
7.8
作者：
Janvier, Katy;Kato, Yukio;Boehm, Markus;Rose, Jeremy R;Martina, Jose A;Kim, Bong-Yoon;Venkatesan, Sundararajan;Bonifacino, Juan S
通讯作者：
Bonifacino, Juan S
DOI：
10.1083/jcb.120.5.1123
发表时间：
1993-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Humphrey JS;Peters PJ;Yuan LC;Bonifacino JS
通讯作者：
Bonifacino JS