title: Deep proteomic evaluation of primary and cell line motoneuron disease models delineates major differences in neuronal characteristics.
abstract: The fatal neurodegenerative disorders amyotrophic lateral sclerosis and spinal muscular atrophy are, respectively, the most common motoneuron disease and genetic cause of infant death. Various in vitro model systems have been established to investigate motoneuron disease mechanisms, in particular immortalized cell lines and primary neurons. Using quantitative mass-spectrometry-based proteomics, we compared 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 used 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 indicated 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 proteins associated with amyotrophic lateral sclerosis 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 mass-spectrometry-based proteomics can be used to evaluate disease model systems.
authors.affiliation: From the ‡Max Planck Institute of Biochemistry, Martinsried, 82152, Germany;
authors.forename: Daniel
authors.initials: D
authors.lastname: Hornburg
authors.affiliation: §Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Wuerzburg, 97080, Wuerzburg, 97078 Germany; ¶Institute for Clinical Neurobiology, Wuerzburg, Germany;
authors.forename: Carsten
authors.initials: C
authors.lastname: Drepper
authors.affiliation: From the ‡Max Planck Institute of Biochemistry, Martinsried, 82152, Germany; ‖Institute of Molecular Biology (IMB), Mainz 55128, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Butter
authors.affiliation: From the ‡Max Planck Institute of Biochemistry, Martinsried, 82152, Germany; meissner@biochem.mpg.de sendtner_M@ukw.de mmann@biochem.mpg.de.
authors.forename: Felix
authors.initials: F
authors.lastname: Meissner
authors.affiliation: ¶Institute for Clinical Neurobiology, Wuerzburg, Germany; meissner@biochem.mpg.de sendtner_M@ukw.de mmann@biochem.mpg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Sendtner
authors.affiliation: From the ‡Max Planck Institute of Biochemistry, Martinsried, 82152, Germany; meissner@biochem.mpg.de sendtner_M@ukw.de mmann@biochem.mpg.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D058977:Molecular Sequence Annotation; D009046:Motor Neurons / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D061251:Primary Cell Culture; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020543:Proteome