A role for presenilins in autophagy revisited: Normal acidification of lysosomes in cells lacking PSEN1 and PSEN2

Xulun Zhang, Krassimira Garbett, Karthikeyan Veeraraghavalu, Brian Wilburn, Reid Gilmore, Karoly Mirnics, Sangram S. Sisodia

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8633-8648
Number of pages16
JournalJournal of Neuroscience
Volume32
Issue number25
DOIs
StatePublished - Jun 20 2012

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Presenilins
Autophagy
Lysosomes
Presenilin-2
Presenilin-1
Vacuolar Proton-Translocating ATPases
Amyloid Precursor Protein Secretases
Brain
Transcriptome
Protons
Catalytic Domain
Alzheimer Disease
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A role for presenilins in autophagy revisited : Normal acidification of lysosomes in cells lacking PSEN1 and PSEN2. / Zhang, Xulun; Garbett, Krassimira; Veeraraghavalu, Karthikeyan; Wilburn, Brian; Gilmore, Reid; Mirnics, Karoly; Sisodia, Sangram S.

In: Journal of Neuroscience, Vol. 32, No. 25, 20.06.2012, p. 8633-8648.

Research output: Contribution to journalArticle

Zhang, Xulun ; Garbett, Krassimira ; Veeraraghavalu, Karthikeyan ; Wilburn, Brian ; Gilmore, Reid ; Mirnics, Karoly ; Sisodia, Sangram S. / A role for presenilins in autophagy revisited : Normal acidification of lysosomes in cells lacking PSEN1 and PSEN2. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 25. pp. 8633-8648.
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