P04 - Role of TRPML channels in endolysosomal cation homeostasis
The TRPML channels are non-selective cation channels expressed in the endolysosomal system. While some of the biophysical properties of TRPMLs have been uncovered recently, the cellular processes and physiological functions which TRPMLs are involved in remain poorly understood. In particular, potential roles of these channels in the regulation of endolysomal vesicle trafficking/fusion, endolysosomal pH control, and endolysosomal cation homeostasis remain elusive. This proposal aims at addressing these important issues on the molecular, cellular and whole-animal level.
a, MK6-83 evoked currents in lysosomes isolated from fibroblasts of a healthy human patient (TRPML1-/-) and a patient with a mutation in TRPML1 leading to the loss of TRPML1 expression (TRPML1-/-) causing the lysosomal storage disorder mucolipidosis type IV. Shown are representative currents elicited in lysosomes after stimulation with the small molecule MK6-83. b, Cartoon showing the lysosomal patch-clamp configuration.