The amyloid precursor protein controls PIKfyve function

While the Amyloid Precursor Protein (APP) plays a central role in Alzheimer's disease, its cellular function still remains largely unclear. It was our goal to establish APP function which will provide insights into APP's implication in Alzheimer's disease. Using our recently developed proteo-liposome assay we established the interactome of APP's intracellular domain (known as AICD), thereby identifying novel APP interactors that provide mechanistic insights into APP function. By combining biochemical, cell biological and genetic approaches we validated the functional significance of one of these novel interactors. Here we show that APP binds the PIKfyve complex, an essential kinase for the synthesis of the endosomal phosphoinositide phosphatidylinositol-3,5-bisphosphate. This signalling lipid plays a crucial role in endosomal homeostasis and receptor sorting. Loss of PIKfyve function by mutation causes profound neurodegeneration in mammals. Using C. elegans genetics we demonstrate that APP functionally cooperates with PIKfyve in vivo. This regulation is required for maintaining endosomal and neuronal function. Our findings establish an unexpected role for APP in the regulation of endosomal phosphoinositide metabolism with dramatic consequences for endosomal biology and important implications for our understanding of Alzheimer's disease

The effect of space vector modulation algorithm on characteristics of three-phase voltage inverter for drives of optical telescopes

The effect of space vector modulation algorithm on magnitude of current vector ripples was considered on the mathematical model of a three-level three-phase voltage inverter with symmetric active inductive load. Limitations on the use of such inverters as a power supply for precision drive of optical telescopes were specified

The effect of space vector modulation algorithm on characteristics of three-phase voltage inverter for drives of optical telescopes

The effect of space vector modulation algorithm on magnitude of current vector ripples was considered on the mathematical model of a three-level three-phase voltage inverter with symmetric active inductive load. Limitations on the use of such inverters as a power supply for precision drive of optical telescopes were specified

Outbreak Of Pleural Mesothelioma And Chronic Fibrosing Pleurisy In Village Of Karain-Urgup In Anatolia

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