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Cell. 2015 Aug 27;162(5):1101-12. doi: 10.1016/j.cell.2015.08.002.

TMEM175 Is an Organelle K(+) Channel Regulating Lysosomal Function.

Author information

1
Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, PA 19104, USA.
2
Paris Descartes University, Sorbonne Paris Cité, Neurophotonics Laboratory, Centre National de la Recherche Scientifique UMR8250, 45 rue des Saints Pères, 75006 Paris, France.
3
Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, PA 19104, USA. Electronic address: dren@sas.upenn.edu.

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.

PMID:
26317472
DOI:
10.1016/j.cell.2015.08.002
[Indexed for MEDLINE]
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