Published February 14, 2024
| Version v1
Journal article
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A mechanism of lysosomal calcium entry
Creators
- 1. University of Chicago
Description
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 RNA interference screen in Caenorhabditis 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, 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 previously unidentified avenues to explore the physiology of Ca2+ channels.
Data availability
All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Raw data are deposited in Dryad: doi:10.5061/dryad.95x69p8rb.
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sciadv.adk2317.pdf
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Additional details
Identifiers
- DOI
- 10.1126/sciadv.adk2317
- Other
- oai:uchicago.tind.io:11102
Funding
- National Institutes of Health
- R21NS114428
- National Institutes of Health
- 1R01NS112139-01A1
- National Institutes of Health
- DP1GM149751
- National Institute of General Medical Sciences
- R01GM147197
- Air Force Office of Scientific Research
- FA9550-19-0003
- National Heart, Lung, and Blood Institute
- R21HL161825-01A1
- Human Frontier Science Program
- RGP0032/2022