{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T04:14:33Z","timestamp":1768536873856,"version":"3.49.0"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030_212795"],"award-info":[{"award-number":["310030_212795"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["CRII5_198543\/2"],"award-info":[{"award-number":["CRII5_198543\/2"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Multidisciplinary Center for Infectious Diseases","award":["MA_09"],"award-info":[{"award-number":["MA_09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Malaria remains a major global health burden, and the emergence of resistance to blood stage antimalarials underscores the need for new interventions targeting earlier stages of the parasite\u2019s life cycle. The pre-erythrocytic liver stage represents a critical bottleneck and an attractive target for chemotherapeutic and prophylactic interventions. In this study, we functionally characterized the putative E3 ubiquitin ligase Trophozoite Exported Protein 1 (TEX1; PBANKA_0102200) in Plasmodium berghei using gene knockout, tagging, and imaging approaches across the mosquito and liver stages. TEX1 knockout parasites (PbTEX1-KO) showed impaired development during mosquito-stage transitions, with significant reductions in ookinete formation, oocyst numbers, and sporozoites reaching the salivary glands. In hepatic stages, TEX1-KO parasites displayed reduced growth, abnormal nuclear division, and impaired liver stage maturation, ultimately leading to a dramatic decline in detached cell formation and blood stage infectivity. Endogenous C-terminal tagging of TEX1 with GFP and 3\u00d7HA revealed a discrete subnuclear localization pattern, indicating a critical role in DNA synthesis and\/or mitotic regulation. Our findings reveal that TEX1 is required for nuclear replication and division and successful development in both the mosquito and liver stages of Plasmodium. Given its pivotal role and nuclear localization during hepatic schizogony, TEX1 represents a promising target for the development of liver stage antimalarial interventions.<\/jats:p>","DOI":"10.3390\/cells15020155","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:13:21Z","timestamp":1768475601000},"page":"155","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Putative E3 Ubiquitin Ligase TEX1 Is Required for Nuclear Biology and Developmental Progression of Plasmodium berghei in the Liver"],"prefix":"10.3390","volume":"15","author":[{"given":"Melanie","family":"Schmid","sequence":"first","affiliation":[{"name":"Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphael","family":"Golomingi","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6041-4182","authenticated-orcid":false,"given":"Blandine","family":"Franke-Fayard","sequence":"additional","affiliation":[{"name":"Leiden Malaria Research Group, Parasitology, Center of Infectious Diseases, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reto","family":"Caldelari","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"Rehmann","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magali","family":"Roques","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volker T.","family":"Heussler","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022, January 18). 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