SorLA/LR11 regulates processing of amyloid precursor protein via interaction with adaptors GGA and PACS-1

被引：143

作者：

Schmidt, Vanessa ^{[1
]}

Sporbert, Anje ^{[1
]}

Rohe, Michael ^{[1
]}

Reimer, Tatjana ^{[1
]}

Rehm, Armin ^{[1
]}

Andersen, Olav M. ^{[1
]}

Willnow, Thomas E. ^{[1
]}

机构：

[1] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2007年 / 282卷 / 45期

关键词：

D O I：

10.1074/jbc.M705073200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

SorLA has been recognized as a novel sorting receptor that regulates trafficking and processing of the amyloid precursor protein (APP) and that represents a significant risk factor for sporadic Alzheimer disease. Here, we investigated the cellular mechanisms that control intracellular trafficking of sorLA and their relevance for APP processing. We demonstrate that sorLA acts as a retention factor for APP in trans-Golgi compartments/trans-Golgi network, preventing release of the precursor into regular processing pathways. Proper localization and activity of sorLA are dependent on functional interaction with GGA and PACS-1, adaptor proteins involved in protein transport to and from the trans-Golgi network. Aberrant targeting of sorLA to the recycling compartment or the plasma membrane causes faulty APP trafficking and imbalance in non-amyloidogenic and amyloidogenic processing fates. Thus, our findings identified altered routing of sorLA as a major cellular mechanism contributing to abnormal APP processing and enhanced amyloid alpha-peptide formation.

引用

页码：32956 / 32964

页数：9

共 34 条

[1] Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11 [J].