Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes

Accumulation of extracellular amyloid beta peptide (Abeta), generated from amyloid precursor protein (APP) processing by beta- and gamma-secretases, is toxic to neurons and is central to the pathogenesis of Alzheimer disease. Production of Abeta from APP is greatly affected by the subcellular locali...

Descripción completa

Detalles Bibliográficos
Autores: Lee, J, Retamal, C., Cuitiño, L., Caruano-Yzermans, A, Shin, J.E., Van Kerkhof, P, Marzolo,M.P., Bu, G.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2008
País:Chile
Idioma:inglés
OAI Identifier:oai:repositorio.anid.cl:10533/237192
Acceso en línea:https://hdl.handle.net/10533/237192
Access Level:acceso abierto
id CL_ac0bad008dc0b2fef00db94f253a5659
oai_identifier_str oai:repositorio.anid.cl:10533/237192
network_acronym_str CL
network_name_str Chile
repository_id_str
spelling Bu, G.Marzolo,M.P.Van Kerkhof, PShin, J.E.Caruano-Yzermans, ACuitiño, L.Retamal, C.Lee, J200810.1074/jbc.M800642200https://hdl.handle.net/10533/237192http://purl.org/coar/access_right/c_abf2Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomesLee, JRetamal, C.Cuitiño, L.Caruano-Yzermans, AShin, J.E.Van Kerkhof, PMarzolo,M.P.Bu, G.2019-12-18T18:14:58Z2022-07-07T22:06:34Z2019-12-18T18:14:58Z2022-07-07T22:06:34Z2008Accumulation of extracellular amyloid beta peptide (Abeta), generated from amyloid precursor protein (APP) processing by beta- and gamma-secretases, is toxic to neurons and is central to the pathogenesis of Alzheimer disease. Production of Abeta from APP is greatly affected by the subcellular localization and trafficking of APP. Here we have identified a novel intracellular adaptor protein, sorting nexin 17 (SNX17), that binds specifically to the APP cytoplasmic domain via the YXNPXY motif that has been shown previously to bind several cell surface adaptors, including Fe65 and X11. Overexpression of a dominant-negative mutant of SNX17 and RNA interference knockdown of endogenous SNX17 expression both reduced steady-state levels of APP with a concomitant increase in Abeta production. RNA interference knockdown of SNX17 also decreased APP half-life, which led to the decreased steady-state levels of APP. Immunofluorescence staining confirmed a colocalization of SNX17 and APP in the early endosomes. We also showed that a cell surface adaptor protein, Dab2, binds to the same YXNPXY motif and regulates APP endocytosis at the cell surface. Our results thus provide strong evidence that both cell surface and intracellular adaptor proteins regulate APP endocytic trafficking and processing to Abeta. The identification of SNX17 as a novel APP intracellular adaptor protein highly expressed in neurons should facilitate the understanding of the relationship between APP intracellular trafficking and processing to Abeta.FONDAPFONDAP1398000113980001virtual::32820-1WOS:000255067400049https://hdl.handle.net/10533/237192enginstname: Conicytreponame: Repositorio Digital RI2.010.1074/jbc.M800642200info:eu-repo/grantAgreement/Fondap/13980001https://www.ncbi.nlm.nih.gov/pubmed/18276590Atribución-NoComercial-SinDerivadas 3.0 Chilehttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/info:eu-repo/semantics/openAccessAdaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomesJ Biol ChemArticuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttps://hdl.handle.net/10533/237192http://purl.org/coar/resource_type/c_2df8fbb14c0c28ba-308a-47c1-afb7-2607f38e4c08virtual::32820-14c0c28ba-308a-47c1-afb7-2607f38e4c08virtual::32820-110533/237192oai:repositorio.anid.cl:10533/2371922023-07-24 17:13:34.708https://repositorio.anid.clRepositorio ANIDaletelier@anid.cl
dc.title.none.fl_str_mv Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes
dc.title.journal.none.fl_str_mv J Biol Chem
title Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes
spellingShingle Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes
Lee, J
title_short Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes
title_full Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes
title_fullStr Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes
title_full_unstemmed Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes
title_sort Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes
dc.creator.none.fl_str_mv Lee, J
Retamal, C.
Cuitiño, L.
Caruano-Yzermans, A
Shin, J.E.
Van Kerkhof, P
Marzolo,M.P.
Bu, G.
author Lee, J
author_facet Lee, J
Retamal, C.
Cuitiño, L.
Caruano-Yzermans, A
Shin, J.E.
Van Kerkhof, P
Marzolo,M.P.
Bu, G.
author_role author
author2 Retamal, C.
Cuitiño, L.
Caruano-Yzermans, A
Shin, J.E.
Van Kerkhof, P
Marzolo,M.P.
Bu, G.
author2_role author
author
author
author
author
author
author
description Accumulation of extracellular amyloid beta peptide (Abeta), generated from amyloid precursor protein (APP) processing by beta- and gamma-secretases, is toxic to neurons and is central to the pathogenesis of Alzheimer disease. Production of Abeta from APP is greatly affected by the subcellular localization and trafficking of APP. Here we have identified a novel intracellular adaptor protein, sorting nexin 17 (SNX17), that binds specifically to the APP cytoplasmic domain via the YXNPXY motif that has been shown previously to bind several cell surface adaptors, including Fe65 and X11. Overexpression of a dominant-negative mutant of SNX17 and RNA interference knockdown of endogenous SNX17 expression both reduced steady-state levels of APP with a concomitant increase in Abeta production. RNA interference knockdown of SNX17 also decreased APP half-life, which led to the decreased steady-state levels of APP. Immunofluorescence staining confirmed a colocalization of SNX17 and APP in the early endosomes. We also showed that a cell surface adaptor protein, Dab2, binds to the same YXNPXY motif and regulates APP endocytosis at the cell surface. Our results thus provide strong evidence that both cell surface and intracellular adaptor proteins regulate APP endocytic trafficking and processing to Abeta. The identification of SNX17 as a novel APP intracellular adaptor protein highly expressed in neurons should facilitate the understanding of the relationship between APP intracellular trafficking and processing to Abeta.
publishDate 2008
dc.date.issued.none.fl_str_mv 2008
dc.date.accessioned.none.fl_str_mv 2019-12-18T18:14:58Z
2022-07-07T22:06:34Z
dc.date.available.none.fl_str_mv 2019-12-18T18:14:58Z
2022-07-07T22:06:34Z
dc.type.none.fl_str_mv Articulo
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.openaire.none.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.folio.none.fl_str_mv 13980001
13980001
dc.identifier.idwos.none.fl_str_mv WOS:000255067400049
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10533/237192
identifier_str_mv 13980001
WOS:000255067400049
url https://hdl.handle.net/10533/237192
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv instname: Conicyt
reponame: Repositorio Digital RI2.0
dc.relation.doi.none.fl_str_mv 10.1074/jbc.M800642200
dc.relation.projectid.none.fl_str_mv info:eu-repo/grantAgreement/Fondap/13980001
dc.relation.uri.none.fl_str_mv https://www.ncbi.nlm.nih.gov/pubmed/18276590
dc.rights.none.fl_str_mv Atribución-NoComercial-SinDerivadas 3.0 Chile
http://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rights.driver.none.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv Atribución-NoComercial-SinDerivadas 3.0 Chile
http://creativecommons.org/licenses/by-nc-nd/3.0/cl/
eu_rights_str_mv openAccess
repository.name.fl_str_mv Repositorio ANID
repository.mail.fl_str_mv aletelier@anid.cl
_version_ 1843518754288304128
score 15.812429

Similares en LA Referencia