Retromer binds the FANSHY sorting motif in SorLA to regulate amyloid precursor protein sorting and processing

sorLA is a sorting receptor for amyloid precursor protein (APP) genetically linked to Alzheimer's disease (AD). Retromer, an adaptor complex in the endosome-to-Golgi retrieval pathway, has been implicated in APP transport because retromer deficiency leads to aberrant APP sorting and processing and levels of retromer proteins are altered in AD. Here we report that sorLA and retromer functionally interact in neurons to control trafficking and amyloidogenic processing of APP. We have identified a sequence (FANSHY) in the cytoplasmic domain of sorLA that is recognized by the VPS26 subunit of the retromer complex. Accordingly, we characterized the interaction between the retromer complex and sorLA and determined the role of retromer on sorLA-dependent sorting and processing of APP. Mutations in the VPS26 binding site resulted in receptor redistribution to the endosomal network, similar to the situation seen in cells with VPS26 knockdown. The sorLA mutant retained APP-binding activity but, as opposed to the wild-type receptor, misdirected APP into a distinct non-Golgi compartment, resulting in increased amyloid processing. In conclusion, our data provide a molecular link between reduced retromer expression and increased amyloidogenesis as seen in patients with sporadic AD

Bread from heaven; a spiritual diet of the sayings of Jesus Christ,

Arranged as a daily study for five years.Mode of access: Internet.MAIN; 984e.M644.b: Letter inserted

Book review: <i>Visuelle Geographien: Zur Produktion, Aneignung und Vermittlung von RaumBildern</i>

No abstract available

Investigation on natural durability and sorption properties of Italian Chestnut (Castanea sativa Mill.) from coppice stands

Castanea sativa Mill. from coppice stands in Italy were evaluated. Fungi trials with different white rot, brown rot and soft rot fungi showed, that the heartwood of chestnut can be classified following EN 350 in durability class 2 as ¿durable¿. However, the durability within the tested material (between trees and planks) can vary considerably. The highest reported durability was class 1 (very durable), whereas other samples were classified as ¿non-durable¿ (class 5). Under soil conditions, where soft rot organism are active, the variation within the tested collective was lower, however resulting in an average ¿moderate durability¿ (class 3). No statistical provable difference between juvenile wood and mature wood was detected. Furthermore, sorption properties and subsequent shrinkage and swelling were determined. Mature wood shows somewhat higher sorption properties and transverse shrinkage/swelling values than juvenile wood. However, longitudinal shrinkage is higher for juvenile woo