{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T07:19:06Z","timestamp":1773127146781,"version":"3.50.1"},"reference-count":78,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Italian MUR, Proof of Concept","award":["POC01_00072"],"award-info":[{"award-number":["POC01_00072"]}]},{"name":"the Italian MUR, Proof of Concept","award":["GGP15083"],"award-info":[{"award-number":["GGP15083"]}]},{"name":"the TELETHON Foundation","award":["POC01_00072"],"award-info":[{"award-number":["POC01_00072"]}]},{"name":"the TELETHON Foundation","award":["GGP15083"],"award-info":[{"award-number":["GGP15083"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lysosomes are acidic Ca2+ storage organelles that actively generate local Ca2+ signaling events to regulate a plethora of cell functions. Here, we characterized lysosomal Ca2+ signals in mouse renal collecting duct (CD) cells and we assessed their putative role in aquaporin 2 (AQP2)-dependent water reabsorption. Bafilomycin A1 and ML-SA1 triggered similar Ca2+ oscillations, in the absence of extracellular Ca2+, by alkalizing the acidic lysosomal pH or activating the lysosomal cation channel mucolipin 1 (TRPML1), respectively. TRPML1-dependent Ca2+ signals were blocked either pharmacologically or by lysosomes\u2019 osmotic permeabilization, thus indicating these organelles as primary sources of Ca2+ release. Lysosome-induced Ca2+ oscillations were sustained by endoplasmic reticulum (ER) Ca2+ content, while bafilomycin A1 and ML-SA1 did not directly interfere with ER Ca2+ homeostasis per se. TRPML1 activation strongly increased AQP2 apical expression and depolymerized the actin cytoskeleton, thereby boosting water flux in response to an hypoosmotic stimulus. These effects were strictly dependent on the activation of the Ca2+\/calcineurin pathway. Conversely, bafilomycin A1 led to perinuclear accumulation of AQP2 vesicles without affecting water permeability. Overall, lysosomal Ca2+ signaling events can be differently decoded to modulate Ca2+-dependent cellular functions related to the dock\/fusion of AQP2-transporting vesicles in principal cells of the CD.<\/jats:p>","DOI":"10.3390\/ijms24021647","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T02:04:45Z","timestamp":1673834685000},"page":"1647","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["TRPML1-Induced Lysosomal Ca2+ Signals Activate AQP2 Translocation and Water Flux in Renal Collecting Duct Cells"],"prefix":"10.3390","volume":"24","author":[{"given":"Simona Ida","family":"Scorza","sequence":"first","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Milano","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilenia","family":"Saponara","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maira","family":"Certini","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"De Zio","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4421-9237","authenticated-orcid":false,"given":"Maria Grazia","family":"Mola","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0043-7523","authenticated-orcid":false,"given":"Giuseppe","family":"Procino","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Carmosino","sequence":"additional","affiliation":[{"name":"Department of Sciences, University of Basilicata, 85100 Potenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0010-0098","authenticated-orcid":false,"given":"Francesco","family":"Moccia","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology Lazzaro Spallanzani, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Svelto","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2839-0130","authenticated-orcid":false,"given":"Andrea","family":"Gerbino","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"403272","DOI":"10.1155\/2010\/403272","article-title":"Molecular mechanisms of receptor-mediated endocytosis in the renal proximal tubular epithelium","volume":"2010","author":"Saito","year":"2010","journal-title":"J. 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