Dataset Information

Precisely measured protein lifetimes in the mouse

ABSTRACT: The turnover of brain proteins is critical for organism survival, and its perturbations are strongly linked to pathology. Nevertheless, precise 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. We solved this problem rigorously by developing a novel workflow that combines mouse in vivo isotopic labeling with mass spectrometry and mathematical modeling. We also established several independent approaches to test and validate the results. This enabled us to measure, for the first time, 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 catalogue of stable proteins, including novel extremely long-lived proteins (ELLPs).

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Sunit Mandad

LAB HEAD: Silvio O. Rizzoli

PROVIDER: PXD010859 | Pride | 2018-11-15

REPOSITORIES: Pride

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			Action	DRS
	PRIDE-ZI.RAR	Other
	S_Mandad_050914_031215_G4_L23_1.raw	Raw
	S_Mandad_050914_031215_G4_L23_10.raw	Raw
	S_Mandad_050914_031215_G4_L23_11.raw	Raw
	S_Mandad_050914_031215_G4_L23_12.raw	Raw

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

Fornasiero Eugenio F EF Mandad Sunit S Wildhagen Hanna H Alevra Mihai M Rammner Burkhard B Keihani Sarva S Opazo Felipe F Urban Inga I Ischebeck Till T Sakib M Sadman MS Fard Maryam K MK Kirli Koray K Centeno Tonatiuh Pena TP Vidal Ramon O RO Rahman Raza-Ur RU Benito Eva E Fischer André A Dennerlein Sven S Rehling Peter P Feussner Ivo I Bonn Stefan S Simons Mikael M Urlaub Henning H Rizzoli Silvio O SO

Nature communications 20181012 1

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 meas ...[more]

PMID: 30315172

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