A mechanism of lysosomal calcium entry

Lysosomal calcium (Ca2+) release is critical to cell signaling and is mediated by well-known lysosomal Ca2+ channels. Yet, how lysosomes refill their Ca2+ remains hitherto undescribed. Here, from an RNAi screen in C. elegans we identify an evolutionarily conserved gene, lci-1, that facilitates lysosomal Ca2+ entry in C. elegans and mammalian cells. We found that its human homolog TMEM165, previously designated as a Ca2+/H+ exchanger (CAX), imports Ca2+ pH-dependently into lysosomes. Using two-ion mapping and electrophysiology we show that TMEM165, hereafter referred to as human LCI, acts as a proton-activated, lysosomal Ca2+ importer. Defects in lysosomal Ca2+ channels cause several neurodegenerative diseases, and knowledge of lysosomal Ca2+ importers may provide new avenues to explore the physiology of Ca2+ channels., , , # A mechanism of lysosomal calcium entry

Raw Data for Manuscript adk2317

Dataset contains fluorescent images, gels, plates, and quantitation from those data.

## Description of the data and file structure

Data is organized by type of experiment. Within each experimental folder, there is an excel spreadsheet that contains the data plotted in the relevant figure (named on the excel sheet tab). There are also subfolders for individual data sets, which contain raw images, gels, and plates.

The \"Electrophysiology\" folder and \"Whole Cell Electrophysiology Raw Data\" folders contain spreadsheets of I-V plot data points for lysosome and whole-cell electrophysiology experiments, respectively. The \"Gels\" folder contains images of full gels from indicated RT-PCR experiments.

The \"Mammalian Cell Cytosolic Ca\" folder contains raw images of HeLa or COS7 cells labeled with the calcium-sensitive fluorophore Fura Red, under the indicated treatments. It also contains spreadsheets showing the calcul...