Intricate effects of primary motor neuronopathy on contractile proteins and metabolic muscle enzymes as revealed by label-free mass spectrometry. Issue 4 (1st July 2014)

• Record Type: Journal Article
• Authors: Holland, Ashling; Schmitt-John, Thomas; Dowling, Paul; Meleady, Paula; Henry, Michael; Clynes, Martin; Ohlendieck, Kay
• Is Part Of: Bioscience reports. Volume 34:Issue 4(2014)
• Publication Date: 2014-07-01
• Subjects: amyotrophic lateral sclerosis -- motor neuron disease -- muscle proteomics -- muscular atrophy -- skeletal muscle proteome -- wobbler mouse; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20140029
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract : The systematic biochemical analysis of muscle from the wobbler mouse model of motor neuron disease suggests that the loss of neuromuscular synapses causes complex changes in the protein profile of contractile tissues, affecting especially the contractile apparatus and energy metabolism. 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.