Lysosomal calcium homeostasis defects, not proton pump defects, cause endo-lysosomal dysfunction in PSEN-deficient cells.

Coen, K. Flannagan, R.S., Carraro-Lacroix, L.R., Wang, D., Vermeire, W., Michiels, C. Munck, S., Sugita, S., Hiesinger, P.R. Grinstein, S., Annaert, W.— 2012

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.

TitelLysosomal calcium homeostasis defects, not proton pump defects, cause endo-lysosomal dysfunction in PSEN-deficient cells.
VerfasserCoen, K. Flannagan, R.S., Carraro-Lacroix, L.R., Wang, D., Vermeire, W., Michiels, C. Munck, S., Sugita, S., Hiesinger, P.R. Grinstein, S., Annaert, W.
VerlagRockefeller University Press
Datum20120709
Kennungdoi: 10.1083/jcb.201201076
Quelle/n
Erschienen inJ. Cell Biol., 198(1):23-35
Spracheeng
ArtText
Rechte© 2012 Coen et al. Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).