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

Eugenio F. Fornasiero (), Sunit Mandad, Hanna Wildhagen, Mihai Alevra, Burkhard Rammner, Sarva Keihani, Felipe Opazo, Inga Urban, Till Ischebeck, M. Sadman Sakib, Maryam K. Fard, Koray Kirli, Tonatiuh Pena Centeno, Ramon O. Vidal, Raza-Ur Rahman, Eva Benito, André Fischer, Sven Dennerlein, Peter Rehling, Ivo Feussner, Stefan Bonn, Mikael Simons, Henning Urlaub () and Silvio O. Rizzoli ()
Additional contact information
Eugenio F. Fornasiero: University Medical Center Göttingen, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain
Sunit Mandad: University Medical Center Göttingen, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain
Hanna Wildhagen: University Medical Center Göttingen, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain
Mihai Alevra: University Medical Center Göttingen, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain
Burkhard Rammner: University Medical Center Göttingen, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain
Sarva Keihani: University Medical Center Göttingen, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain
Felipe Opazo: University Medical Center Göttingen, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain
Inga Urban: Max Planck Institute of Biophysical Chemistry
Till Ischebeck: Georg-August-University
M. Sadman Sakib: German Center for Neurodegenerative Diseases (DZNE)
Maryam K. Fard: German Center for Neurodegenerative Disease (DZNE)
Koray Kirli: Max Planck Institute for Biophysical Chemistry
Ramon O. Vidal: German Center for Neurodegenerative Diseases (DZNE)
Raza-Ur Rahman: German Center for Neurodegenerative Diseases (DZNE)
Eva Benito: German Center for Neurodegenerative Diseases (DZNE)
André Fischer: German Center for Neurodegenerative Diseases (DZNE)
Sven Dennerlein: University Medical Center Göttingen
Peter Rehling: University Medical Center Göttingen
Ivo Feussner: Georg-August-University
Stefan Bonn: German Center for Neurodegenerative Diseases (DZNE)
Mikael Simons: German Center for Neurodegenerative Disease (DZNE)
Henning Urlaub: University Medical Center Göttingen
Silvio O. Rizzoli: University Medical Center Göttingen, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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).

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (8)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06519-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06519-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06519-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().