title: Aberrant Subcellular Dynamics of Sigma-1 Receptor Mutants Underlying Neuromuscular Diseases.
abstract: The sigma-1 receptor (σ-1R) is an endoplasmic reticulum resident chaperone protein involved in a plethora of cellular functions, and whose disruption has been implicated in a wide range of diseases. Genetic analysis has revealed two σ-1R mutants involved in neuromuscular disorders. A point mutation (E102Q) in the ligand-binding domain results in the juvenile form of amyotrophic lateral sclerosis (ALS16), and a 20 amino-acid deletion (Δ31-50) in the putative cytosolic domain leads to a form of distal hereditary motor neuropathy. We investigated the localization and functional properties of these mutants in cell lines using confocal imaging and electrophysiology. The σ-1R mutants exhibited a significant increase in mobility, aberrant localization, and enhanced block of the inwardly rectifying K(+) channel Kir2.1, compared with the wild-type σ-1R. Thus, these σ-1R mutants have different functional properties that could contribute to their disease phenotypes.
authors.affiliation: Neuroscience, Ottawa Hospital Research Institute, Ottawa (A.Y.C.W., E.H., N.A., L.-A.T., J.K.N, P.C., R.B.), and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa (J.K.N., R.B.), Ontario, Canada.
authors.forename: Adrian Y C
authors.initials: AY
authors.lastname: Wong
authors.affiliation: Neuroscience, Ottawa Hospital Research Institute, Ottawa (A.Y.C.W., E.H., N.A., L.-A.T., J.K.N, P.C., R.B.), and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa (J.K.N., R.B.), Ontario, Canada.
authors.forename: Elitza
authors.initials: E
authors.lastname: Hristova
authors.affiliation: Neuroscience, Ottawa Hospital Research Institute, Ottawa (A.Y.C.W., E.H., N.A., L.-A.T., J.K.N, P.C., R.B.), and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa (J.K.N., R.B.), Ontario, Canada.
authors.forename: Nina
authors.initials: N
authors.lastname: Ahlskog
authors.affiliation: Neuroscience, Ottawa Hospital Research Institute, Ottawa (A.Y.C.W., E.H., N.A., L.-A.T., J.K.N, P.C., R.B.), and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa (J.K.N., R.B.), Ontario, Canada.
authors.forename: Louis-Alexandre
authors.initials: LA
authors.lastname: Tasse
authors.affiliation: Neuroscience, Ottawa Hospital Research Institute, Ottawa (A.Y.C.W., E.H., N.A., L.-A.T., J.K.N, P.C., R.B.), and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa (J.K.N., R.B.), Ontario, Canada.
authors.forename: Johnny K
authors.initials: JK
authors.lastname: Ngsee
authors.affiliation: Neuroscience, Ottawa Hospital Research Institute, Ottawa (A.Y.C.W., E.H., N.A., L.-A.T., J.K.N, P.C., R.B.), and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa (J.K.N., R.B.), Ontario, Canada.
authors.forename: Prakash
authors.initials: P
authors.lastname: Chudalayandi
authors.affiliation: Neuroscience, Ottawa Hospital Research Institute, Ottawa (A.Y.C.W., E.H., N.A., L.-A.T., J.K.N, P.C., R.B.), and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa (J.K.N., R.B.), Ontario, Canada rbergeron@ohri.ca.
authors.forename: Richard
authors.initials: R
authors.lastname: Bergeron
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism*; D009468:Neuromuscular Diseases / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D051669:Shab Potassium Channels / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D000097605:Sigma-1 Receptor
chemical_list: D050505:Mutant Proteins; D017480:Receptors, sigma; D011993:Recombinant Fusion Proteins; D051669:Shab Potassium Channels; D000097605:Sigma-1 Receptor