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Series GSE44454 Query DataSets for GSE44454
Status Public on Dec 15, 2017
Title Presenilins mediate endosomal recycling via ARF6 to maintain proper lysosomal clearance
Organism Mus musculus
Experiment type Expression profiling by array
Summary Autophagic and endosomal dysfunctions are prominently observed at preclinical stages of Alzheimer's disease (AD) as well as in presenilin (PSEN) 1-deficient mice and neurons. In the latter, the defects relate to the γ-secretase-independent role of PSEN in lysosomal fusion and organelle turnover. While we demonstrated previously that the impaired capacity of lysosomal fusion is associated with a significant reduction in lysosomal calcium storage/release, the underlying mechanism remained unexplored. Here we demonstrate that PSEN-deficient cells are impaired in endosomal recycling of several cargo proteins reminiscent of clathrin-independent carriers and lipid rafts. This is accompanied by the accumulation of cholesterol in LAMP1-positive organelles. The small GTPase ARF6, an important regulator of lipid raft recycling, fully rescues the endo-lysosomal abnormalities in PSEN-/- cells, suggesting that defective recycling is upstream of lysosomal dysfunction. PSEN-/- cells and neurons present significantly reduced ARF6 expression levels. Importantly, similar decreased ARF6 levels are observed in aging murine neurons and brain and are even more pronounced in AD brains, suggesting a particular vulnerability of ARF6-mediated recycling in the early etiology of AD.
Overall design 4 cell lines were analyzed from 3 biological replicates. These samples include MEF wild-type, MEF PSEN1&2-/-, MEF PSEN1&2-/- retrovirally transduced with hARF6, and MEF PSEN1&2-/- retrovirally transduced with hPSEN1 D257A/D385A mutant.
Contributor(s) Coen K, Munck S, Raghunath A, Raemaekers T, Vermeire W, Flannagan RS, Declerck I, Baert V, Grinstein S, Wuytack F, Delacourte A, Rajendran L, Eskelinen E, Gevaert K, Annaert W
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Submission date Feb 21, 2013
Last update date Dec 15, 2017
Contact name Rekin's Janky
Organization name VIB
Department Nucleomics Core
Street address Herestraat 49 Box 816
City Leuven
ZIP/Postal code B-3000
Country Belgium
Platforms (1)
GPL11202 Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version)
Samples (12)
GSM1085653 11820
GSM1085654 11821
GSM1085655 11822
BioProject PRJNA190192

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Supplementary file Size Download File type/resource
GSE44454_RAW.tar 181.6 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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