@article {Wongmol.116.104018, author = {Adrian YC Wong and Elitza Hristova and Nina Ahlskog and Louis-Alexandre Tasse and Johnny Ngsee and Prakash Chudalayandi and Richard Bergeron}, title = {ABERRANT SUBCELLULAR DYNAMICS OF SIGMA-1 RECEPTOR MUTANTS UNDERLYING NEUROMUSCULAR DISEASES}, elocation-id = {mol.116.104018}, year = {2016}, doi = {10.1124/mol.116.104018}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The Sigma-1 Receptor (σ-1R) is an endoplasmic reticulum (ER) 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 site 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 (dHMN). 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 WT σ-1R. Thus, these σ-1R mutants have different functional properties that could contribute to their disease phenotypes.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/early/2016/07/14/mol.116.104018}, eprint = {https://molpharm.aspetjournals.org/content/early/2016/07/14/mol.116.104018.full.pdf}, journal = {Molecular Pharmacology} }