TY - JOUR
T1 - A role for presenilins in autophagy revisited
T2 - Normal acidification of lysosomes in cells lacking PSEN1 and PSEN2
AU - Zhang, Xulun
AU - Garbett, Krassimira
AU - Veeraraghavalu, Karthikeyan
AU - Wilburn, Brian
AU - Gilmore, Reid
AU - Mirnics, Karoly
AU - Sisodia, Sangram S.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/6/20
Y1 - 2012/6/20
N2 - Presenilins 1 and 2 (PS1 and PS2) are the catalytic subunits of the-secretase complex, and genes encoding mutant PS1 and PS2 variants cause familial forms of Alzheimer's disease. Lee et al. (2010) recently reported that loss of PS1 activity lead to impairments in autophagosomal function as a consequence of lysosomal alkalinization, caused by failed maturation of the proton translocating V0a1 subunit of the vacuolar (H+)-ATPase and targeting to the lysosome. We have reexamined these issues in mammalian cells and in brains of mice lacking PS (PScdko) and have been unable to find evidence that the turnover of autophagic substrates, vesicle pH, V0a1 maturation, or lysosome function is altered compared with wild-type counterparts. Collectively, our studies fail to document a role for presenilins in regulating cellular autophagosomal function. On the other hand, our transcriptome studies of PScdko mouse brains reveal, for the first time, a role for PS in regulating lysosomal biogenesis.
AB - Presenilins 1 and 2 (PS1 and PS2) are the catalytic subunits of the-secretase complex, and genes encoding mutant PS1 and PS2 variants cause familial forms of Alzheimer's disease. Lee et al. (2010) recently reported that loss of PS1 activity lead to impairments in autophagosomal function as a consequence of lysosomal alkalinization, caused by failed maturation of the proton translocating V0a1 subunit of the vacuolar (H+)-ATPase and targeting to the lysosome. We have reexamined these issues in mammalian cells and in brains of mice lacking PS (PScdko) and have been unable to find evidence that the turnover of autophagic substrates, vesicle pH, V0a1 maturation, or lysosome function is altered compared with wild-type counterparts. Collectively, our studies fail to document a role for presenilins in regulating cellular autophagosomal function. On the other hand, our transcriptome studies of PScdko mouse brains reveal, for the first time, a role for PS in regulating lysosomal biogenesis.
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U2 - 10.1523/JNEUROSCI.0556-12.2012
DO - 10.1523/JNEUROSCI.0556-12.2012
M3 - Article
C2 - 22723704
AN - SCOPUS:84862883617
VL - 32
SP - 8633
EP - 8648
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 25
ER -