A growth-factor-activated lysosomal K⁺ channel regulates Parkinson's pathology.

ABSTRACT: Lysosomes have fundamental physiological roles and have previously been implicated in Parkinson's disease^1-5. However, how extracellular growth factors communicate with intracellular organelles to control lysosomal function is not well understood. Here we report a lysosomal K⁺ channel complex that is activated by growth factors and gated by protein kinase B (AKT) that we term lysoK_GF. LysoK_GF consists of a pore-forming protein TMEM175 and AKT: TMEM175 is opened by conformational changes in, but not the catalytic activity of, AKT. The minor allele at rs34311866, a common variant in TMEM175, is associated with an increased risk of developing Parkinson's disease and reduces channel currents. Reduction in lysoK_GF function predisposes neuro

SUBMITTER: Wie J 

PROVIDER: S-EPMC7979525 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature