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

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• dc.contributor.author Lachén Montes, Mercedes
• dc.contributor.author Mendizuri, Naroa
• dc.contributor.author Ausín, Karina
• dc.contributor.author Pérez Mediavilla, Alberto
• dc.contributor.author Azkargorta, Mikel
• dc.contributor.author Iloro, Ibon
• dc.contributor.author Elortza, Félix
• dc.contributor.author Kondo, Hiroyuki
• dc.contributor.author Ohigashi, Izumi
• dc.contributor.author Ferrer, Isidre
• dc.contributor.author Torre Fornell, Rafael de la
• dc.contributor.author Robledo, Patricia, 1958-
• dc.contributor.author Fernández Irigoyen, Joaquín
• dc.contributor.author Santamaría, Enrique
• dc.date.accessioned 2021-01-14T07:12:52Z
• dc.date.available 2021-01-14T07:12:52Z
• dc.date.issued 2020
• dc.description.abstract The 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Lachén-Montes M, Mendizuri N, Ausín K, Pérez-Mediavilla A, Azkargorta M, Iloro I, Elortza F, Kondo H, Ohigashi I, Ferrer I, de la Torre R, Robledo P, Fernández-Irigoyen J, Santamaría E. Smelling the dark proteome: functional characterization of PITH domain-containing protein 1 (C1orf128) in olfactory metabolism. J Proteome Res. 2020; 19(12):4826-43. DOI: 10.1021/acs.jproteome.0c00452
• dc.identifier.doi http://dx.doi.org/10.1021/acs.jproteome.0c00452
• dc.identifier.issn 1535-3893
• dc.identifier.uri http://hdl.handle.net/10230/46164
• dc.language.iso eng
• dc.publisher American Chemical Society (ACS)
• dc.relation.ispartof J Proteome Res. 2020; 19(12):4826-43
• 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.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html
• dc.subject.keyword Human proteome project
• dc.subject.keyword PITHD1
• dc.subject.keyword Dark proteome
• dc.subject.keyword Neurodegeneration
• dc.subject.keyword Olfaction
• dc.subject.keyword uPE1
• dc.title Smelling the dark proteome: functional characterization of PITH domain-containing protein 1 (C1orf128) in olfactory metabolism
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion