title: TMEM175 Is an Organelle K(+) Channel Regulating Lysosomal Function.
abstract: 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.
authors: Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, PA 19104, USA.
authors: Chunlei
authors: C
authors: Cang
authors: Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, PA 19104, USA.
authors: Kimberly
authors: K
authors: Aranda
authors: Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, PA 19104, USA.
authors: Young-jun
authors: YJ
authors: Seo
authors: Paris Descartes University, Sorbonne Paris Cité, Neurophotonics Laboratory, Centre National de la Recherche Scientifique UMR8250, 45 rue des Saints Pères, 75006 Paris, France.
authors: Bruno
authors: B
authors: Gasnier
authors: Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, PA 19104, USA. Electronic address: dren@sas.upenn.edu.
authors: Dejian
authors: D
authors: Ren
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010588:Phagosomes / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D015221:Potassium Channels; C000602835:TMEM175 protein, human; C000602834:TMEM175 protein, mouse; D011188:Potassium