TY - JOUR T1 - Aberrant Subcellular Dynamics of Sigma-1 Receptor Mutants Underlying Neuromuscular Diseases JF - Molecular Pharmacology JO - Mol Pharmacol SP - 238 LP - 253 DO - 10.1124/mol.116.104018 VL - 90 IS - 3 AU - Adrian Y. C. Wong AU - Elitza Hristova AU - Nina Ahlskog AU - Louis-Alexandre Tasse AU - Johnny K. Ngsee AU - Prakash Chudalayandi AU - Richard Bergeron Y1 - 2016/09/01 UR - http://molpharm.aspetjournals.org/content/90/3/238.abstract N2 - 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. ER -