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. |