Dataset Information

Molecular signatures of membrane protein complexes underlying muscular dystrophy

ABSTRACT: Mutations in genes encoding components of the sarcolemmal dystrophin-glycoprotein complex (DGC) are responsible for a large number of muscular dystrophies. As such, molecular dissection of the DGC is expected to both reveal pathological mechanisms, and provides a biological framework for validating new DGC components. Establishment of the molecular composition of plasma-membrane protein complexes has been hampered by a lack of suitable biochemical approaches. Here we present an analytical workflow based upon the principles of protein correlation profiling that has enabled us to model the molecular composition of plasma-membrane protein complexes in mouse skeletal muscle. We also report our analysis of protein complexes in mice harboring mutations in DGC components, which implicates cell-adhesion pathways directly targeted by NFκB in the pathophysiology of DGC-related muscular dystrophies. Our study suggests that inflammatory and compensatory mechanisms are activated in these diseases. Additionally, it provides a molecular framework that will facilitate refinement of our understanding of the DGC, identification of protein biomarkers of neuromuscular disease, and pharmacological interrogation of the DGC in adult skeletal muscle.

INSTRUMENT(S): 6520 Quadrupole Time-of-Flight LC/MS

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Skeletal Muscle

SUBMITTER: Jordy Hsiao

LAB HEAD: Michael Eugene Wright

PROVIDER: PXD002846 | Pride | 2020-03-12

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	061711_dirMS_WT_4_120.d.zip	Other
	061711_dirMS_WT_4_120.pep.xml	Pepxml
	061711_dirMS_WT_4_30.d.zip	Other
	061711_dirMS_WT_4_30.pep.xml	Pepxml
	061711_dirMS_WT_4_60.d.zip	Other

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Publications

Molecular Signatures of Membrane Protein Complexes Underlying Muscular Dystrophy.

Turk Rolf R Hsiao Jordy J JJ Smits Melinda M MM Ng Brandon H BH Pospisil Tyler C TC Jones Kayla S KS Campbell Kevin P KP Wright Michael E ME

Molecular & cellular proteomics : MCP 20160420 6

Mutations in genes encoding components of the sarcolemmal dystrophin-glycoprotein complex (DGC) are responsible for a large number of muscular dystrophies. As such, molecular dissection of the DGC is expected to both reveal pathological mechanisms, and provides a biological framework for validating new DGC components. Establishment of the molecular composition of plasma-membrane protein complexes has been hampered by a lack of suitable biochemical approaches. Here we present an analytical workfl ...[more]

PMID: 27099343

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