Quantitative Map of Proteome Dynamics during Neuronal Differentiation.
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.
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 Utrecht, the Netherlands.
Christian K
CK
Frese
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands.
Marina
M
Mikhaylova
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 Utrecht, the Netherlands; Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands.
Riccardo
R
Stucchi
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 Utrecht, the Netherlands.
Violette
V
Gautier
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 Utrecht, the Netherlands; Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands.
Qingyang
Q
Liu
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 Utrecht, the Netherlands.
Shabaz
S
Mohammed
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 Utrecht, the Netherlands.
Albert J R
AJR
Heck
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 Utrecht, the Netherlands. Electronic address: m.altelaar@uu.nl.
A F Maarten
AFM
Altelaar
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands. Electronic address: c.hoogenraad@uu.nl.
Casper C
CC
Hoogenraad
D000199:Actins / Q000378:metabolism; D000818:Animals; D019002:CD56 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002853:Chromatography, Liquid / Q000379:methods; D003712:Dendrites / Q000378:metabolism / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D007553:Isotope Labeling / Q000379:methods; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D051381:Rats; D053719:Tandem Mass Spectrometry / Q000379:methods
D000199:Actins; D019002:CD56 Antigen; D020543:Proteome
NCAM1; adhesion molecule; dendrite outgrowth; mass spectrometry; neuronal development; neuronal differentiation; neuroproteomics; proteome; quantitative proteomics; stable isotope labeling