The Study On Amyloid Precursor Protein's Trafficking Mechanism

Alzheimer's diseases(AD)which acts as a neurodegenerative disease,has great negative influence to patients and patients' family.More and more biochemical and genetic evidences show that amyloid precursor protein(APP)has a very important role in the pathogenesis of AD.APP is a type I transmembrane protein which is similar to a cell surface receptor,with a large extracellular N-terminal structural domain and a short cytoplasmic tail.Although the study of the APP focuses on the C-terminal,a large number of evidences show that the N-terminal of the APP is able to regulate the trafficking and processing of its own.Inherent disordered area within the N-terminal also increases the possibility and mystery of the regulating.In recent years,the research on the inherent disorder protein(IDP)show that it can affect the protein half-life,timely protein structure changing and protein-protein interactions regulation.By using the methods of transient expression,we found that the lack of IDP could reduce the production of SAPP.In order to further explore the underlying mechanism of this phenomenon,by using intensity correlation quotient(ICQ)showed the colocalization with golgi apparatus was significantly different between the wild type APP and the disorder domain deletion APP,whereas in endoplasmic reticulum there was no difference,and the disorder domain deletion APP quantity did not elevate at trans-golgi apparatus like the wild type.We also found the deletion of ACD domain was not going to effect the quantity of APP and SAPP in endosome with N-terminal antibody colocalization.The crude lipid raft extraction experiments indicated that the deletion of ACD domain could cause distribution changing of APP at the surface of the cell from the perspective of the micro-environment of protein location.Until now,we can draw the conclusion that the extracellular domain of APP could regulate the trafficking and processing of APP by APP's distribution in trans-golgi apparatus and location at the cell surface.