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bioRxiv · 10.1101/2023.08.08.552438

TMEM165 acts as a proton-activated Ca2+ importer in lysosomes

Zajac, M.·Mukherjee, S.·Anees, P.·Oettinger, D.·Henn, K.·Srikumar, J.·Zou, J.·Saminathan, A.·Krishnan, Y.
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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 RNAi screen, we identify an evolutionarily conserved gene, lci-1, that facilitates lysosomal Ca2+ entry in C. elegans and in mammalian cells. Its human homolog TMEM165, previously designated as a Golgi-resident Ca2+/H+ exchanger (CAX), has a minor lysosomal population of unknown function. Using genetics, lysosomal Ca2+ imaging and electrophysiology, we show that TMEM165 acts as a proton-activated, lysosomal Ca2+ importer in lysosomes. 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.

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Zajac, M., Mukherjee, S., Anees, P., Oettinger, D., Henn, K., Srikumar, J., Zou, J., Saminathan, A., Krishnan, Y.. 2023-08-09. TMEM165 acts as a proton-activated Ca2+ importer in lysosomes. https://doi.org/10.1101/2023.08.08.552438

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