. Interaction of the cytosolic domains of sorLA/LR11 with the amyloid precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme. J Neurosci. 2006 Jan 11;26(2):418-28. PubMed.

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  1. It is great to see the continuation of the work on sorLA. The authors previously found that this protein influences APP shedding and Aβ generation, both under overexpression and knockout conditions. Their new work sheds more light on the underlying molecular mechanisms. In contrast to many soluble, cytoplasmic proteins that can bind APP and alter APP shedding, sorLA is one of very few membrane proteins that have been reported to coimmunoprecipitate with APP. The authors propose that sorLA interferes with complex formation between APP and BACE1. It will be interesting to see how exactly sorLA interacts with APP/C99 and BACE1, and whether the interaction is mediated through the transmembrane domains or through the cytoplasmic domains. Potentially, sorLA may also interact with the other APP secretases, in particular with the ADAM proteases.