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Title: Lysosomal calcium homeostasis defects, not proton pump defects, cause endo-lysosomal dysfunction in PSEN-deficient cells
Authors: Coen, Katrijn
Flannagan, Ronald S
Baron, Szilvia
Carraro-Lacroix, Luciene R
Wang, Dong
Vermeire, Wendy
Michiels, Christine
Munck, Sebastian
Baert, Veerle
Sugita, Shuzo
Wuytack, Frank
Hiesinger, Peter Robin
Grinstein, Sergio
Annaert, Wim # ×
Issue Date: 9-Jul-2012
Publisher: Rockefeller Institute Press
Series Title: Journal of Cell Biology vol:198 issue:1 pages:23-35
Article number: 22753898
Abstract: Presenilin (PSEN) deficiency is accompanied by accumulation of endosomes and autophagosomes, likely caused by impaired endo-lysosomal fusion. Recently, Lee et al. (2010. Cell. doi: http://dx.doi.org/10.1016/j.cell.2010.05.008) attributed this phenomenon to PSEN1 enabling the transport of mature V0a1 subunits of the vacuolar ATPase (V-ATPase) to lysosomes. In their view, PSEN1 mediates the N-glycosylation of V0a1 in the endoplasmic reticulum (ER); consequently, PSEN deficiency prevents V0a1 glycosylation, compromising the delivery of unglycosylated V0a1 to lysosomes, ultimately impairing V-ATPase function and lysosomal acidification. We show here that N-glycosylation is not a prerequisite for proper targeting and function of this V-ATPase subunit both in vitro and in vivo in Drosophila melanogaster. We conclude that endo-lysosomal dysfunction in PSEN(-/-) cells is not a consequence of failed N-glycosylation of V0a1, or compromised lysosomal acidification. Instead, lysosomal calcium storage/release is significantly altered in PSEN(-/-) cells and neurons, thus providing an alternative hypothesis that accounts for the impaired lysosomal fusion capacity and accumulation of endomembranes that accompanies PSEN deficiency.
URI: 
ISSN: 0021-9525
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory of Cellular Transport Systems
Laboratory of Membrane Trafficking
× corresponding author
# (joint) last author

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