MassIVE MSV000084939

Imported Reanalysis Dataset Public PXD000666

Deep proteomic evaluation of primary and cell line motoneuron disease models delineates major differences in neuronal characteristics

Description

The fatal neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are the most common motoneuron disease and genetic cause of infant death, respectively. Various in vitro model systems have been established to investigate motoneuron disease mechanisms - in particular immortalized cell lines and primary neurons. By quantitative mass spectrometry (MS)-based proteomics we here compare the proteomes of primary motoneurons to motoneuron-like cell lines NSC-34 and N2a as well as to non-neuronal control cells at a depth of 10,000 proteins. We use this resource to evaluate the suitability of murine in vitro model systems for cell biological and biochemical analysis of motoneuron disease mechanisms. Individual protein and pathway analysis indicate substantial differences between motoneuron-like cell lines and primary motoneurons, especially for proteins involved in differentiation, cytoskeleton and receptor signaling, whereas common metabolic pathways were more similar. The ALS-associated proteins themselves also showed distinct differences between cell lines and primary motoneurons, providing a molecular basis for understanding fundamental alterations between cell lines and neurons with respect to neuronal pathways with relevance for disease mechanisms. Our study provides a proteomics resource for motoneuron research and presents a paradigm of how MS-based proteomics can be used to evaluate disease model systems [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: neurodegeneration ; quantitative proteomics ; neuron ; motoneuron ; amyotrophic lateral sclerosis ; ALS ; ; MassIVE.quant reviewed - Gold

Contact

Principal Investigators:
(in alphabetical order)
Matthias Mann, Department of Proteomics and Signal Transduction Max Planck Institute of Biochemistry, N/A
Submitting User: ccms

Publications

Hornburg D, Drepper C, Butter F, Meissner F, Sendtner M, Mann M.
Deep proteomic evaluation of primary and cell line motoneuron disease models delineates major differences in neuronal characteristics.
Mol. Cell Proteomics. 2014 Dec;13(12):3410-20. Epub 2014 Sep 5.

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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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