Presenilins interact with Rab11, a small GTPase involved in the regulation of vesicular transport

Presenilins interact with Rab11, a small GTPase involved in the regulation of vesicular transport
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DOI:
10.1093/hmg/8.7.1263
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发表时间:
1999-07-01
影响因子:
3.5
通讯作者:
Frebourg, T
Frebourg, T
中科院分区:
生物学2区
文献类型:
--
作者:
Dumanchin, C;Czech, C;Frebourg, T

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早老素1(PS1)突变占家族性阿尔茨海默病早发显性病例的大多数。早老素(Presenilins,PS)分布于细胞内的内质网、高尔基体、核区和泡状结构等。这些蛋白质包括7至9个假定的跨膜结构域,具有N-和C-末端和朝向细胞质的大亲水环。我们报道了人PS 1或PS 2亲水环与Ras相关超家族的小GTP酶Rab 11之间的相互作用。相互作用域被定位到PS 1的密码子374-400和Rab 11的密码子106-179,Rab 11是包括第四个GTP结合域的区域。考虑到Rab蛋白在囊泡转运途径中的意义,PS-Rab 11相互作用表明PS可能参与淀粉样前体蛋白囊泡路由。
Presenilin 1 (PS1) mutations account for the majority of early-onset dominant cases of familial Alzheimer's disease. Presenilins (PSs) are located in many intracellular compartments such as the endoplasmic reticulum, Golgi apparatus, nuclear region and vesicular structures. These proteins include from seven to nine putative transmembrane domains, with the N- and C-terminal ends and a large hydrophilic loop orientated towards the cytoplasm. We report an interaction between the human PS1 or PS2 hydrophilic loop and Rab11, a small GTPase belonging to the Ras-related superfamily, Interaction domains were mapped to codons 374-400 for PS1 and to codons 106-179 for Rab11, a region including the fourth GTP-binding domain. Considering the implication of Rab proteins in vesicular transport pathways, the PS-Rab11 interaction suggests that PSs might be involved in amyloid precursor protein vesicular routing.