Proteasome stress leads to APP axonal transport defects by promoting its amyloidogenic processing in lysosomes
Alzheimer disease (AD) pathology includes the accumulation of poly-ubiquitylated (also known as poly-ubiquitinated) proteins and failures in proteasome-dependent degradation. Whereas the distribution of proteasomes and its role in synaptic function have been studied, whether proteasome activity regu...
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| Formato: | Capítulo de libro |
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Company of Biologists Ltd
2018
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| Acceso en línea: | Registro en Scopus DOI Handle Registro en la Biblioteca Digital |
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| LEADER | 25145caa a22019457a 4500 | ||
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| 001 | PAPER-25195 | ||
| 003 | AR-BaUEN | ||
| 005 | 20230518205712.0 | ||
| 008 | 190410s2018 xx ||||fo|||| 00| 0 eng|d | ||
| 024 | 7 | |2 scopus |a 2-s2.0-85048343214 | |
| 024 | 7 | |2 cas |a proteasome, 140879-24-9 | |
| 040 | |a Scopus |b spa |c AR-BaUEN |d AR-BaUEN | ||
| 030 | |a JNCSA | ||
| 100 | 1 | |a Otero, M.G. | |
| 245 | 1 | 0 | |a Proteasome stress leads to APP axonal transport defects by promoting its amyloidogenic processing in lysosomes |
| 260 | |b Company of Biologists Ltd |c 2018 | ||
| 270 | 1 | 0 | |m Falzone, T.L.; Instituto de Biologiá Celular y Neurociencias IBCN (CONICET-UBA), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Argentina; email: tfalzone@fmed.uba.ar |
| 506 | |2 openaire |e Política editorial | ||
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| 520 | 3 | |a Alzheimer disease (AD) pathology includes the accumulation of poly-ubiquitylated (also known as poly-ubiquitinated) proteins and failures in proteasome-dependent degradation. Whereas the distribution of proteasomes and its role in synaptic function have been studied, whether proteasome activity regulates the axonal transport and metabolism of the amyloid precursor protein (APP), remains elusive. By using live imaging in primary hippocampal neurons, we showed that proteasome inhibition rapidly and severely impairs the axonal transport of APP. Fluorescence cross-correlation analyses andmembrane internalization blockage experiments showed that plasma membrane APP does not contribute to transport defects. Moreover, by western blotting and double-color APP imaging, we demonstrated that proteasome inhibition precludes APP axonal transport by enhancing its endo-lysosomal delivery, where β- cleavage is induced. Taken together, we found that proteasomes control the distal transport of APP and can re-distribute Golgi-derived vesicles to the endo-lysosomal pathway. This crosstalk between proteasomes and lysosomes regulates the intracellular APP dynamics, and defects in proteasome activity can be considered a contributing factor that leads to abnormal APP metabolism in AD. © 2018. Published by The Company of Biologists Ltd. |l eng | |
| 536 | |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas | ||
| 536 | |a Detalles de la financiación: U.S. Department of Defense, AZ140064 | ||
| 536 | |a Detalles de la financiación: Universidad de Buenos Aires, UBACyT 2011/2014 | ||
| 536 | |a Detalles de la financiación: Ministerio de Ciencia, Tecnología e Innovación Productiva, PICT 2013-0402 | ||
| 536 | |a Detalles de la financiación: Ministerio de Ciencia, Tecnología e Innovación Productiva | ||
| 536 | |a Detalles de la financiación: NIRG10-172840 | ||
| 536 | |a Detalles de la financiación: This work was supported by grants from the Ministerio de Ciencia, Tecnologıá e Innovación Productiva (MINCyT) (PICT 2013-0402, T.L.F.); the Alzheimer’s Association (NIRG10-172840, T.L.F.); the Universidad de Buenos Aires (UBACyT 2011/2014, T.L.F.); and the U.S. Department of Defense (AZ140064, A.A.-Q.). M.G.O., T.M.S. and L.E.C. acknowledge support from Consejo Nacional de Investigaciones Cientıf́ icas y Técnicas (CONICET) fellowships. | ||
| 593 | |a Instituto de Biologiá Celular y Neurociencias IBCN (CONICET-UBA), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires, CP1121, Argentina | ||
| 593 | |a Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Quimíca Biológica-IQUIBICEN UBA-CONICET, Buenos Aires, CP1428EGA, Argentina | ||
| 593 | |a Instituto de Biología y Medicina Experimental, IBYME (CONICET), Vuelta de obligado 2490, Buenos Aires, CP 1428, Argentina | ||
| 593 | |a Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, United States | ||
| 690 | 1 | 0 | |a ALZHEIMER DISEASE |
| 690 | 1 | 0 | |a AMYLOID PRECURSOR PROTEIN |
| 690 | 1 | 0 | |a AXONAL TRANSPORT |
| 690 | 1 | 0 | |a LYSOSOME |
| 690 | 1 | 0 | |a PROTEASOME |
| 690 | 1 | 0 | |a AMYLOID PRECURSOR PROTEIN |
| 690 | 1 | 0 | |a PROTEASOME |
| 690 | 1 | 0 | |a ANIMAL CELL |
| 690 | 1 | 0 | |a ANIMAL TISSUE |
| 690 | 1 | 0 | |a ARTICLE |
| 690 | 1 | 0 | |a CELL MEMBRANE |
| 690 | 1 | 0 | |a CONTROLLED STUDY |
| 690 | 1 | 0 | |a FLUORESCENCE ANALYSIS |
| 690 | 1 | 0 | |a GOLGI COMPLEX |
| 690 | 1 | 0 | |a HIPPOCAMPUS |
| 690 | 1 | 0 | |a LIVE CELL IMAGING |
| 690 | 1 | 0 | |a LYSOSOME |
| 690 | 1 | 0 | |a MOLECULAR INTERACTION |
| 690 | 1 | 0 | |a MOUSE |
| 690 | 1 | 0 | |a NERVE CELL |
| 690 | 1 | 0 | |a NERVE FIBER TRANSPORT |
| 690 | 1 | 0 | |a NEWBORN |
| 690 | 1 | 0 | |a NONHUMAN |
| 690 | 1 | 0 | |a PRIORITY JOURNAL |
| 690 | 1 | 0 | |a PROTEIN AGGREGATION |
| 690 | 1 | 0 | |a PROTEIN DEGRADATION |
| 690 | 1 | 0 | |a PROTEIN LOCALIZATION |
| 690 | 1 | 0 | |a PROTEIN METABOLISM |
| 690 | 1 | 0 | |a PROTEIN PROCESSING |
| 690 | 1 | 0 | |a PROTEIN TRANSPORT |
| 690 | 1 | 0 | |a WESTERN BLOTTING |
| 700 | 1 | |a Bessone, I.F. | |
| 700 | 1 | |a Hallberg, A.E. | |
| 700 | 1 | |a Cromberg, L.E. | |
| 700 | 1 | |a De Rossi, M.C. | |
| 700 | 1 | |a Saez, T.M. | |
| 700 | 1 | |a Levi, V. | |
| 700 | 1 | |a Almenar-Queralt, A. | |
| 700 | 1 | |a Falzone, T.L. | |
| 773 | 0 | |d Company of Biologists Ltd, 2018 |g v. 131 |k n. 11 |p J. Cell Sci. |x 00219533 |w (AR-BaUEN)CENRE-769 |t Journal of Cell Science | |
| 856 | 4 | 1 | |u https://www.scopus.com/inward/record.uri?eid=2-s2.0-85048343214&doi=10.1242%2fjcs214536&partnerID=40&md5=dd1414a6bf168a5a99964c6245a26232 |y Registro en Scopus |
| 856 | 4 | 0 | |u https://doi.org/10.1242/jcs214536 |y DOI |
| 856 | 4 | 0 | |u https://hdl.handle.net/20.500.12110/paper_00219533_v131_n11_p_Otero |y Handle |
| 856 | 4 | 0 | |u https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219533_v131_n11_p_Otero |y Registro en la Biblioteca Digital |
| 961 | |a paper_00219533_v131_n11_p_Otero |b paper |c PE | ||
| 962 | |a info:eu-repo/semantics/article |a info:ar-repo/semantics/artículo |b info:eu-repo/semantics/publishedVersion | ||
| 999 | |c 86148 | ||