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  Precisely measured protein lifetimes in the mouse brain reveal differences across tissues and subcellular fractions.

Fornasiero, E. F., Mandad, S., Wildhagen, H., Alevra, M., Rammner, B., Keihani, S., et al. (2018). Precisely measured protein lifetimes in the mouse brain reveal differences across tissues and subcellular fractions. Nature Communications, 9: 4230. doi:10.1038/s41467-018-06519-0.

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Fornasiero, E. F., Author
Mandad, S.1, Author           
Wildhagen, H., Author
Alevra, M., Author
Rammner, B., Author
Keihani, S., Author
Opazo, F., Author
Urban, I.2, Author           
Ischebeck, T., Author
Sakib, M. S., Author
Fard, M. K., Author
Kirli, K., Author
Centeno, T. P., Author
Vidal, R. O., Author
Rahman, R. U., Author
Benito, E., Author
Fischer, A., Author
Dennerlein, S., Author
Rehling, P.3, Author           
Feussner, I., Author
Bonn, S., AuthorSimons, M., AuthorUrlaub, H.1, Author           Rizzoli, S. O., Author more..
Affiliations:
1Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              
2Department of Genes and Behavior, MPI for Biophysical Chemistry, Max Planck Society, ou_persistent34              
3Max Planck Fellow Peter Rehling, ou_1298545              

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 Abstract: The turnover of brain proteins is critical for organism survival, and its perturbations are linked to pathology. Nevertheless, protein lifetimes have been difficult to obtain in vivo. They are readily measured in vitro by feeding cells with isotopically labeled amino acids, followed by mass spectrometry analyses. In vivo proteins are generated from at least two sources: labeled amino acids from the diet, and non-labeled amino acids from the degradation of pre-existing proteins. This renders measurements difficult. Here we solved this problem rigorously with a workflow that combines mouse in vivo isotopic labeling, mass spectrometry, and mathematical modeling. We also established several independent approaches to test and validate the results. This enabled us to measure the accurate lifetimes of ~3500 brain proteins. The high precision of our data provided a large set of biologically significant observations, including pathway-, organelle-, organ-, or cell-specific effects, along with a comprehensive catalog of extremely long-lived proteins (ELLPs).

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Language(s): eng - English
 Dates: 2018-10-12
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-018-06519-0
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Title: Nature Communications
Source Genre: Journal
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Pages: 17 Volume / Issue: 9 Sequence Number: 4230 Start / End Page: - Identifier: -