A voltage-dependent K+ channel in the lysosome is required for refilling lysosomal Ca2+ stores

• DOI: 10.1083/jcb.201612123
• Publication Date: 2017-05-03T14:10:10Z
• Authors: Wuyang Wang; Xiaoli Zhang; Qiong Gao; Maria Lawas; Lu Yu; Xiping Cheng; Mingxue Gu; Nirakar Sahoo; Xinran Li; Ping Li; Stephen Ireland; Andrea Meredith; Haoxing Xu
• Keywords: Mice, Knockout; 0301 basic medicine; Time Factors; Genotype; Endoplasmic Reticulum; Membrane Potentials; Protein Transport; 03 medical and health sciences; Cholesterol; HEK293 Cells; Phenotype; Potassium Channels, Voltage-Gated; Cell Line, Tumor; COS Cells; Chlorocebus aethiops; Potassium Channel Blockers; Animals; Humans; Calcium; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Lysosomes; Ion Channel Gating; Research Articles

The resting membrane potential (Δψ) of the cell is negative on cytosolic side and determined primarily by plasma membrane’s selective permeability to K+. We show that lysosomal Δψ set permeabilities Na+ H+, but not K+, positive side. An increase in juxta-lysosomal Ca2+ rapidly reversed activating a large voltage-dependent K+-selective conductance (LysoKVCa). LysoKVCa encoded molecularly SLO1 proteins known for forming BK channels. Opening single channels sufficient cause rapid, striking changes Δψ. Lysosomal stores may be refilled from endoplasmic reticulum (ER) via ER–lysosome contact sites. propose serves as perilysosomal effector prime lysosomes refilling process. Consistently, genetic ablation or pharmacological inhibition LysoKVCa, abolition its sensitivity, blocks maintenance stores, resulting cholesterol accumulation lysosome storage phenotype.