TMEM175 Is an Organelle K+ Channel Regulating Lysosomal Function
2015
Cang, Chunlei | Aranda, Kimberly | Seo, Young-jun | Gasnier, Bruno | Ren, Dejian
Potassium is the most abundant ion to face both plasma and organelle membranes. Extensive research over the past seven decades has characterized how K+ permeates the plasma membrane to control fundamental processes such as secretion, neuronal communication, and heartbeat. However, how K+ permeates organelles such as lysosomes and endosomes is unknown. Here, we directly recorded organelle K+ conductance and discovered a major K+-selective channel KEL on endosomes and lysosomes. KEL is formed by TMEM175, a protein with unknown function. Unlike any of the ∼80 plasma membrane K+ channels, TMEM175 has two repeats of 6-transmembrane-spanning segments and has no GYG K+ channel sequence signature-containing, pore-forming P loop. Lysosomes lacking TMEM175 exhibit no K+ conductance, have a markedly depolarized ΔΨ and little sensitivity to changes in [K+], and have compromised luminal pH stability and abnormal fusion with autophagosomes during autophagy. Thus, TMEM175 comprises a K+ channel that underlies the molecular mechanism of lysosomal K+ permeability.
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