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Title: Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway
Authors: Esselens, Carl
Oorschot, Viola
Baert, Veerle
Raemaekers, Tim
Spittaels, Kurt
Serneels, Lutgarde
Zheng, Hui
Saftig, Paul
De Strooper, Bart
Klumperman, Judith
Annaert, Wim # ×
Issue Date: Sep-2004
Publisher: Rockefeller Institute Press
Series Title: Journal of Cell Biology vol:166 issue:7 pages:1041-54
Abstract: Presenilin 1 (PS1) interacts with telencephalin (TLN) and the amyloid precursor protein via their transmembrane domain (Annaert, W.G., C. Esselens, V. Baert, C. Boeve, G. Snellings, P. Cupers, K. Craessaerts, and B. De Strooper. 2001. Neuron. 32:579-589). Here, we demonstrate that TLN is not a substrate for gamma-secretase cleavage, but displays a prolonged half-life in PS1(-/-) hippocampal neurons. TLN accumulates in intracellular structures bearing characteristics of autophagic vacuoles including the presence of Apg12p and LC3. Importantly, the TLN accumulations are suppressed by adenoviral expression of wild-type, FAD-linked and D257A mutant PS1, indicating that this phenotype is independent from gamma-secretase activity. Cathepsin D deficiency also results in the localization of TLN to autophagic vacuoles. TLN mediates the uptake of microbeads concomitant with actin and PIP2 recruitment, indicating a phagocytic origin of TLN accumulations. Absence of endosomal/lysosomal proteins suggests that the TLN-positive vacuoles fail to fuse with endosomes/lysosomes, preventing their acidification and further degradation. Collectively, PS1 deficiency affects in a gamma-secretase-independent fashion the turnover of TLN through autophagic vacuoles, most likely by an impaired capability to fuse with lysosomes.
ISSN: 0021-9525
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Laboratory of Membrane Trafficking
Laboratory for the Research of Neurodegenerative Diseases
Department of Human Genetics - miscellaneous
Biomedical Sciences Group Management - miscellaneous
× corresponding author
# (joint) last author

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