TAILIEUCHUNG - Báo cáo khoa học: Proteomic characterization of lipid raft proteins in amyotrophic lateral sclerosis mouse spinal cord

Familial amyotrophic lateral sclerosis (ALS) has been linked to mutations in the copper⁄zinc superoxide dismutase (SOD1) gene. The mutant SOD1 protein exhibits a toxic gain-of-function that adversely affects the function of neurons. However, the mechanism by which mutant SOD1 initiates ALS is unclear. | Proteomic characterization of lipid raft proteins in amyotrophic lateral sclerosis mouse spinal cord Jianjun Zhai1 z Anna-Lena Strỏm1 Renee Kilty1 Priya Venkatakrishnan2 James White3 William V. Everson3 Eric J. Smart3 and Haining Zhu1 2 1 Department of Molecular and Cellular Biochemistry Center for StructuralBiology College of Medicine University of Kentucky Lexington KY USA 2 Graduate Center for Toxicology College of Medicine University of Kentucky Lexington KY USA 3 Department of Pediatrics College of Medicine University of Kentucky Lexington KY USA Keywords amyotrophic lateral sclerosis cytoskeletal dynamics lipid rafts proteomics vesicular trafficking Correspondence H. Zhu Department of Molecular and Cellular Biochemistry College of Medicine University of Kentucky 741 South Limestone Lexington KY 40536 USA Fax 1 859 257 2283 Tel 1 859 323 3643 E-mail haining@ These authors contributed equally to this work Received 7 January 2009 revised 30 March 2009 accepted 8 April2009 doi Familial amyotrophic lateral sclerosis ALS has been linked to mutations in the copper zinc superoxide dismutase SOD1 gene. The mutant SOD1 protein exhibits a toxic gain-of-function that adversely affects the function of neurons. However the mechanism by which mutant SOD1 initiates ALS is unclear. Lipid rafts are specialized microdomains of the plasma membrane that act as platforms for the organization and interaction of proteins involved in multiple functions including vesicular trafficking neurotransmitter signaling and cytoskeletal rearrangements. In this article we report a proteomic analysis using a widely used ALS mouse model to identify differences in spinal cord lipid raft proteomes between mice overexpressing wild-type WT and G93A mutant SOD1. In total 413 and 421 proteins were identified in the lipid rafts isolated from WT and G93A mice respectively. Further quantitative analysis revealed a consortium of proteins with altered levels between .

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