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Smelling the dark proteome: functional characterization of PITH domain-containing protein 1 (C1orf128) in olfactory metabolism

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dc.contributor.authorLachén Montes, Mercedes
dc.contributor.authorMendizuri, Naroa
dc.contributor.authorAusín, Karina
dc.contributor.authorPérez Mediavilla, Alberto
dc.contributor.authorAzkargorta, Mikel
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorSantamaría Martínez, Enrique
dc.contributor.authorIloro, Ibon
dc.contributor.authorElortza, Félix
dc.contributor.authorKondo, Hiroyuki
dc.contributor.authorOhigashi, Izumi
dc.contributor.authorFerrer, Isidro
dc.contributor.authorTorre, Rafael de la
dc.contributor.authorRobledo, Patricia
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernuaes
dc.contributor.funderUniversidad Pública de Navarra / Nafarroako Unibertsitate Publikoaes
dc.date.accessioned2021-06-14T11:17:31Z
dc.date.available2021-06-14T11:17:31Z
dc.date.issued2020
dc.descriptionIncluye material complementarioes_ES
dc.description.abstractThe Human Proteome Project (HPP) consortium aims to functionally characterize the dark proteome. On the basis of the relevance of olfaction in early neurodegeneration, we have analyzed the dark proteome using data mining in public resources and omics data sets derived from the human olfactory system. Multiple dark proteins localize at synaptic terminals and may be involved in amyloidopathies such as Alzheimer's disease (AD). We have characterized the dark PITH domain-containing protein 1 (PITHD1) in olfactory metabolism using bioinformatics, proteomics, in vitro and in vivo studies, and neuropathology. PITHD1-/- mice exhibit olfactory bulb (OB) proteome changes related to synaptic transmission, cognition, and memory. OB PITHD1 expression increases with age in wild-type (WT) mice and decreases in Tg2576 AD mice at late stages. The analysis across 6 neurological disorders reveals that olfactory tract (OT) PITHD1 is specifically upregulated in human AD. Stimulation of olfactory neuroepithelial (ON) cells with PITHD1 alters the ON phosphoproteome, modifies the proliferation rate, and induces a pro-inflammatory phenotype. This workflow applied by the Spanish C-HPP and Human Brain Proteome Project (HBPP) teams across the ON-OB-OT axis can be adapted as a guidance to decipher functional features of dark proteins. Data are available via ProteomeXchange with identifiers PXD018784 and PXD021634.en
dc.description.sponsorshipThis work was funded by grants from the Spanish Ministry of Science Innovation and Universities (ref. PID2019-110356RB-I00 to JFI and ES) and Department of Economic and Business Development from Government of Navarra (ref. 0011-1411-2020-000028) to ES and from MEXT-JSPS 17K08884 and Takeda Science Foundation to IO. The Proteomics Unit of Navarrabiomed is a member of Proteored (PRB3-ISCIII) and is supported by grant PT17/0019/009 to JFI, of the PE I+D+I 2013–2016 funded by ISCIII and FEDER. MLM was supported by a postdoctoral fellowship from the Public University of Navarra (UPNA).en
dc.format.extent18 p.
dc.format.mimetypeapplication/pdfen
dc.identifier.doi10.1021/acs.jproteome.0c00452
dc.identifier.issn1535-3893
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/39901
dc.language.isoengen
dc.publisherACS Publicationsen
dc.relation.ispartofJournal of Proteome Research, 2020, 19, 4826−4843en
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110356RB-I00/ES/en
dc.relation.publisherversionhttps://doi.org/10.1021/acs.jproteome.0c00452
dc.rights© 2020 American Chemical Society. This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License, which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectDark proteomeen
dc.subjectHuman Proteome Projecten
dc.subjectNeurodegenerationen
dc.subjectOlfactionen
dc.subjectPITHD1en
dc.subjectUPE1en
dc.titleSmelling the dark proteome: functional characterization of PITH domain-containing protein 1 (C1orf128) in olfactory metabolismen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dspace.entity.typePublication
relation.isAuthorOfPublicationcc02d7db-8e88-40d1-81e0-834617b4849d
relation.isAuthorOfPublication86d1b76e-4790-40b1-a3ec-72331c5c6199
relation.isAuthorOfPublicationabacfd17-2b93-4d99-bae2-52053d57401e
relation.isAuthorOfPublication.latestForDiscoverycc02d7db-8e88-40d1-81e0-834617b4849d

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