In an exhaustive study, Iwata (240.1) presented evidence that the trans Golgi network was the major site of Aβ42 production in both neural and non-neural cells. Cos-1 and N2a cells were transfected with C100 bearing retention signals for the ER, CGN or TGN. Intracellular and extracellular production of Aβ were then determined by Western blotting or ELISA. Aβ production was wiped out in cells containing C100 which were tagged for ER or CGN retention, whereas Aβ production from cells transfected with C100 bearing a TGN retention signal was indistinguishable from untagged C100 transfectants. Moreover, co-transfection with mtPS2 and TGN-tagged C100 caused a marked increase in intracellular and secreted Aβ, suggesting that PS2 and C100 normally interact at this locus.—Dominic Walsh


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