{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T07:56:55Z","timestamp":1792223815949,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013105","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000}}],"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI156096"],"award-info":[{"award-number":["AI156096"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24POST1196440"],"award-info":[{"award-number":["24POST1196440"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI163140"],"award-info":[{"award-number":["AI163140"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM144545"],"award-info":[{"award-number":["GM144545"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Trypanosoma cruzi<\/jats:italic>, the causative agent of Chagas disease, is a parasitic protist that affects millions of people worldwide. Currently there are no fully effective drugs or vaccines available. Contact of <jats:italic>T. cruzi<\/jats:italic> infective forms with their host cells or with the extracellular matrix increases their intracellular Ca<jats:sup>2+<\/jats:sup> concentration suggesting a mechano-transduction process. We report here that <jats:italic>T. cruzi<\/jats:italic> possesses two distinct mechanosensitive Piezo channels, named TcPiezo1 and TcPiezo2, with different subcellular localizations but similarly essential for normal proliferation, differentiation, and infectivity. While TcPiezo1 localizes to the plasma membrane, TcPiezo2 localizes to the lysosomes. Downregulation of <jats:italic>TcPiezo1<\/jats:italic> expression by a novel ligand-regulated hammerhead ribozyme (HHR) significantly inhibited Ca<jats:sup>2+<\/jats:sup> entry in cells expressing a genetically encoded Ca<jats:sup>2+<\/jats:sup> indicator while downregulation of <jats:italic>TcPiezo2<\/jats:italic> expression inhibited Ca<jats:sup>2+<\/jats:sup> release from lysosomes, which are now identified as novel acidic Ca<jats:sup>2+<\/jats:sup> stores in trypanosomes. The channels are activated by contact with extracellular matrix and by hypoosmotic stress. The results establish the essentiality of Piezo channels for the life cycle and Ca<jats:sup>2+<\/jats:sup> homeostasis of <jats:italic>T. cruzi<\/jats:italic> and a novel lysosomal localization for a Piezo channel in eukaryotes.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013105","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:41:11Z","timestamp":1745430071000},"page":"e1013105","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lysosome and plasma membrane Piezo channels of Trypanosoma cruzi are essential for proliferation, differentiation and infectivity"],"prefix":"10.1371","volume":"21","author":[{"given":"Guozhong","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayara 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