A mechanism of lysosomal calcium entry.

ABSTRACT: 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 Ca

SUBMITTER: Zajac M 

PROVIDER: S-EPMC10866540 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature