title: Intricate effects of primary motor neuronopathy on contractile proteins and metabolic muscle enzymes as revealed by label-free mass spectrometry.
abstract: While the long-term physiological adaptation of the neuromuscular system to changed functional demands is usually reflected by unilateral skeletal muscle transitions, the progressive degeneration of distinct motor neuron populations is often associated with more complex changes in the abundance and/or isoform expression pattern of contractile proteins and metabolic enzymes. In order to evaluate these intricate effects of primary motor neuronopathy on the skeletal muscle proteome, label-free MS was employed to study global alterations in the WR (wobbler) mouse model of progressive neurodegeneration. In motor neuron disease, fibre-type specification and the metabolic weighting of bioenergetic pathways appear to be strongly influenced by both a differing degree of a subtype-specific vulnerability of neuromuscular synapses and compensatory mechanisms of fibre-type shifting. Proteomic profiling confirmed this pathobiochemical complexity of disease-induced changes and showed distinct alterations in 72 protein species, including a variety of fibre-type-specific isoforms of contractile proteins, metabolic enzymes, metabolite transporters and ion-regulatory proteins, as well as changes in molecular chaperones and various structural proteins. Increases in slow myosin light chains and the troponin complex and a decrease in fast MBP (myosin-binding protein) probably reflect the initial preferential loss of the fast type of neuromuscular synapses in motor neuron disease.
authors.affiliation: *Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland.
authors.forename: Ashling
authors.initials: A
authors.lastname: Holland
authors.affiliation: †Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitt-John
authors.affiliation: *Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland.
authors.forename: Paul
authors.initials: P
authors.lastname: Dowling
authors.affiliation: ‡National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Paula
authors.initials: P
authors.lastname: Meleady
authors.affiliation: ‡National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Henry
authors.affiliation: ‡National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Martin
authors.initials: M
authors.lastname: Clynes
authors.affiliation: *Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland.
authors.forename: Kay
authors.initials: K
authors.lastname: Ohlendieck
mesh_terms: D000818:Animals; D003285:Contractile Proteins / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods
chemical_list: D003285:Contractile Proteins; D018832:Molecular Chaperones; D020033:Protein Isoforms; D020543:Proteome