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

First Author  Cang C Year  2015
Journal  Cell Volume  162
Issue  5 Pages  1101-12
PubMed ID  26317472 Mgi Jnum  J:225577
Mgi Id  MGI:5693670 Doi  10.1016/j.cell.2015.08.002
Citation  Cang C, et al. (2015) TMEM175 Is an Organelle K(+) Channel Regulating Lysosomal Function. Cell 162(5):1101-12
abstractText  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 approximately 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 DeltaPsi 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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