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Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway

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 subst...

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Autores principales: Esselens, Cary, Oorschot, Viola, Baert, Veerle, Raemaekers, Tim, Spittaels, Kurt, Serneels, Lutgarde, Zheng, Hui, Saftig, Paul, De Strooper, Bart, Klumperman, Judith, Annaert, Wim
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172014/
https://www.ncbi.nlm.nih.gov/pubmed/15452145
http://dx.doi.org/10.1083/jcb.200406060
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author Esselens, Cary
Oorschot, Viola
Baert, Veerle
Raemaekers, Tim
Spittaels, Kurt
Serneels, Lutgarde
Zheng, Hui
Saftig, Paul
De Strooper, Bart
Klumperman, Judith
Annaert, Wim
author_facet Esselens, Cary
Oorschot, Viola
Baert, Veerle
Raemaekers, Tim
Spittaels, Kurt
Serneels, Lutgarde
Zheng, Hui
Saftig, Paul
De Strooper, Bart
Klumperman, Judith
Annaert, Wim
author_sort Esselens, Cary
collection PubMed
description 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 γ-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 γ-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 γ-secretase–independent fashion the turnover of TLN through autophagic vacuoles, most likely by an impaired capability to fuse with lysosomes.
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spelling pubmed-21720142008-03-05 Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway Esselens, Cary Oorschot, Viola Baert, Veerle Raemaekers, Tim Spittaels, Kurt Serneels, Lutgarde Zheng, Hui Saftig, Paul De Strooper, Bart Klumperman, Judith Annaert, Wim J Cell Biol Research Articles 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 γ-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 γ-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 γ-secretase–independent fashion the turnover of TLN through autophagic vacuoles, most likely by an impaired capability to fuse with lysosomes. The Rockefeller University Press 2004-09-27 /pmc/articles/PMC2172014/ /pubmed/15452145 http://dx.doi.org/10.1083/jcb.200406060 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Esselens, Cary
Oorschot, Viola
Baert, Veerle
Raemaekers, Tim
Spittaels, Kurt
Serneels, Lutgarde
Zheng, Hui
Saftig, Paul
De Strooper, Bart
Klumperman, Judith
Annaert, Wim
Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway
title Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway
title_full Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway
title_fullStr Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway
title_full_unstemmed Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway
title_short Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway
title_sort presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172014/
https://www.ncbi.nlm.nih.gov/pubmed/15452145
http://dx.doi.org/10.1083/jcb.200406060
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