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To counter membrane attack, diverse eukaryotic cells employ Ca2+-binding penta-EF (PEF)-hand proteins, including the human ortholog, ALG-2, to maintain membrane integrity. Candida albicans is a major fungal pathogen in humans, where increasing resistance to current antifungal drugs that target the plasma membrane is of serious concern. Combinatorial treatments that additionally compromise the plasma membrane offer a way forward, but our mechanistic understanding of how fungi respond to direct membrane disruption remains limited. Here, we investigated the PEF-hand ortholog, Pef1, in this polymorphic species. GFP-tagged Pef1 localized at sites of polarized growth in yeast and hyphal cells of C. albicans. On treatment of hyphae with the polyene drug, amphotericin B, or the saponin tomatine, GFP-Pef1 became distributed as punctate spots at the membrane. In a similar manner, loss of calcineurin A (Cna1), but not of its transcription factor, Crz1, caused this punctate localization pattern of GFP-Pef1. While deletion of PEF1 slightly impaired yeast cell growth rate, filamentation was not affected. Strikingly, pef1\u0394 hyphae could not maintain plasma membrane integrity in serum, as also seen in the cna1\u0394 mutant, and exhibited attenuated virulence in an insect larvae infection model. Together, these observations suggest that Pef1 localizes to sites of membrane perturbation to maintain cell integrity, including sites of dynamic polarized growth, septum formation, and fungicide-induced membrane disruption.<\/jats:p>","DOI":"10.1093\/g3journal\/jkag075","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T17:32:00Z","timestamp":1775064720000},"source":"Crossref","is-referenced-by-count":1,"title":["The penta-EF-hand protein Pef1 of\n                    <i>Candida albicans<\/i>\n                    functions at sites of membrane perturbation to support polarized growth and membrane integrity"],"prefix":"10.1093","volume":"16","author":[{"given":"Martin","family":"Weichert","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Genetik, Technische Universit\u00e4t Braunschweig , Braunschweig 38106 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel Ren\u00e9","family":"Schumann","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Genetik, Technische Universit\u00e4t Braunschweig , Braunschweig 38106 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Brandt","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Genetik, Technische Universit\u00e4t Braunschweig , Braunschweig 38106 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Bedford","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Medical Mycology (MRC CMM) at the University of Exeter , Exeter EX4 4QD ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7381-131X","authenticated-orcid":false,"given":"Alexandra C","family":"Brand","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Medical Mycology (MRC CMM) at the University of Exeter , Exeter EX4 4QD ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Flei\u00dfner","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Genetik, Technische Universit\u00e4t Braunschweig , Braunschweig 38106 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"2026060312315391800_jkag075-B1","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1128\/EC.00008-07","article-title":"Sterol-rich plasma membrane domains in fungi","volume":"6","author":"Alvarez","year":"2007","journal-title":"Eukaryot Cell"},{"key":"2026060312315391800_jkag075-B2","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1093\/femsre\/fuz022","article-title":"Fungal plasma membrane domains","volume":"43","author":"Athanasopoulos","year":"2019","journal-title":"FEMS Microbiol 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