Smelling the dark proteome: functional characterization of PITH domain-containing protein 1 (C1orf128) in olfactory metabolism
| Autor: | Mikel Azkargorta, Felix Elortza, Hiroyuki Kondo, Patricia Robledo, Naroa Mendizuri, Isidre Ferrer, Rafael de la Torre, Karina Ausín, Ibon Iloro, Izumi Ohigashi, Enrique Santamaría, Alberto Pérez-Mediavilla, Mercedes Lachén-Montes, Joaquín Fernández-Irigoyen |
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| Přispěvatelé: | Universidad Pública de Navarra. Departamento de Ciencias de la Salud, Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila, Gobierno de Navarra / Nafarroako Gobernua, Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Proteomics
0301 basic medicine Olfactory system Proteome UPE1 Olfaction Biology Biochemistry Mice 03 medical and health sciences Alzheimer Disease Human proteome project medicine Animals uPE1 Neurodegeneration Human Proteome Project 030102 biochemistry & molecular biology PITHD1 General Chemistry Human brain Olfactory Bulb Olfactory bulb Cell biology Smell 030104 developmental biology medicine.anatomical_structure Dark proteome Olfactory tract |
| Zdroj: | Academica-e: Repositorio Institucional de la Universidad Pública de Navarra Universidad Pública de Navarra Academica-e. Repositorio Institucional de la Universidad Pública de Navarra instname |
| ISSN: | 2019-1103 |
| Popis: | Incluye material complementario 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. This 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). |
| Databáze: | OpenAIRE |
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