Subcellular localization of presenilins: Association with a unique membrane pool in cultured cells

We have investigated the subcellular distribution of presenilin-1 (PS1) and presenilin-2 (PS2) in a variety of mammalian cell lines. In lodixanol-base d density gradients, PS1 derivatives show a biphasic distribution, cofracti onating with membranes containing ER-resident proteins and an additional po pulation of membranes with low buoyant density that do not contain markers of the Golgi complex, ERGIC, COP II vesicles, ER exit compartment, COP II r eceptor, Golgi SNARE, trans-Golgi network, caveolar membranes, or endocytic vesicles. Confocal immunofluorescence and immunoelectron microscopy studie s fully supported the fractionation studies. These data suggest that PS1 fr agments accumulate in a unique subcompartment(s) of the ER or ER to Golgi t rafficking intermediates. Interestingly, the FAD-linked PS1 variants show a marked redistribution toward the heavier region of the gradient. Finally, and in contrast to PS1, PS2 fragments are detected preponderantly in more d ensely sedimenting membranes, suggesting that the subcellular compartments in which these molecules accumulate are distinct. (C) 2000 Academic Press.