Cell Reports
Volume 18, Issue 6, 7 February 2017, Pages 1527-1542
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Quantitative Map of Proteome Dynamics during Neuronal Differentiation

https://doi.org/10.1016/j.celrep.2017.01.025Get rights and content
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Highlights

  • Systematic profile of proteome dynamics throughout neuronal development in vitro

  • Approximately 1,800 proteins show significant expression changes during differentiation

  • Six expression profile clusters describe stage-specific patterns of protein dynamics

  • This protein database may help to identify neurodevelopment mechanisms

Summary

Neuronal differentiation is a multistep process that shapes and re-shapes neurons by progressing through several typical stages, including axon outgrowth, dendritogenesis, and synapse formation. To systematically profile proteome dynamics throughout neuronal differentiation, we took cultured rat hippocampal neurons at different developmental stages and monitored changes in protein abundance using a combination of stable isotope labeling and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). Almost one third of all 4,500 proteins quantified underwent a more than 2-fold expression change during neuronal differentiation, indicating extensive remodeling of the neuron proteome. To highlight the strength of our resource, we studied the neural-cell-adhesion molecule 1 (NCAM1) and found that it stimulates dendritic arbor development by promoting actin filament growth at the dendritic growth cone. We anticipate that our quantitative map of neuronal proteome dynamics is a rich resource for further analyses of the many identified proteins in various neurodevelopmental processes.

Keywords

neuronal differentiation
neuronal development
dendrite outgrowth
neuroproteomics
NCAM1
adhesion molecule
proteome
quantitative proteomics
stable isotope labeling
mass spectrometry

Cited by (0)

4

Co-first author

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Present address: CECAD Research Center, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany

6

Present address: Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany

7

Present address: Evotec France, 195 Route d’Espagne, BP13669, 31036 Toulouse, France

8

Present address: Department of Biochemistry, University of Oxford, South Parks Road, OX13QU Oxford, UK

9

Lead Contact