{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:43:19Z","timestamp":1781844199783,"version":"3.54.5"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008111","name":"Hermann Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008111","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>Plasmodium vivax<\/jats:italic> is the most widespread cause of malaria outside Africa. Developing effective controls is challenging because <jats:italic>P. vivax<\/jats:italic> exclusively invades reticulocytes, immature erythrocytes that are scarce and short-lived. This limits opportunities to culture the parasite and investigate the receptor-ligand interactions crucial for host cell invasion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The erythroid cell lines JK-1 and BEL-A were evaluated <jats:italic>in vitro<\/jats:italic> as reticulocyte surrogates to assess their susceptibility to <jats:italic>P. vivax<\/jats:italic> invasion. Comparative membrane proteomics of these cell lines, reticulocytes, and mature erythrocytes were performed using quantitative liquid chromatography\u2013mass spectrometry (LC-MS). Specific interactions between the parasite ligand PvRBP1a (residues 158\u2013650) and candidate host receptors were identified by TurboID proximity labeling and validated through ELISA binding assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We confirmed that the JK-1 cell line supports <jats:italic>P. vivax<\/jats:italic> invasion and demonstrated for the first time that BEL-A cells are similarly susceptible, establishing both as effective surrogate models. Membrane proteomics identified several receptor candidates potentially involved in selective host-cell entry. In addition to known receptors, including transferrin receptor protein 1 (TfR1\/CD71), CD98hc, and basigin (BSG), novel receptor candidates such as prohibitin-2 (PHB2), CAT-1 (SLC7A1), ATB(0) (SLC1A5), CD36, integrin beta-1 (ITGB1), and metal transporter CNNM3 were discovered. Proximity labeling with a recombinant PvRBP1a (158\u2013650)-TurboID fusion protein confirmed the known interactions with TfR1 and BSG, and additionally identified PHB2 as a novel interacting partner. Notably, this is the first report implicating PHB2 as a co-receptor for <jats:italic>P. vivax<\/jats:italic> invasion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings provide novel insights into the molecular mechanisms underlying reticulocyte restriction in <jats:italic>P. vivax<\/jats:italic>. The JK-1 and BEL-A cell lines represent valuable platforms for dissecting receptor\u2013ligand interactions during parasite invasion and for advancing the development of targeted therapeutic antimalarial strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1671048","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T05:27:20Z","timestamp":1758778040000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The reticulocyte restriction: invasion ligand RBP1a of Plasmodium vivax targets human TfR1, prohibitin-2, and basigin"],"prefix":"10.3389","volume":"15","author":[{"given":"Jessica","family":"Molina-Franky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"R\u00f6th","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Ararat\u2010Sarria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel Alfonso","family":"Patarroyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Kalkum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1002\/1873-3468.12053","article-title":"Host-parasite interaction: multiple sites in the Plasmodium vivax tryptophan-rich antigen PvTRAg38 interact with the erythrocyte receptor band 3","volume":"590","author":"Alam","year":"2016","journal-title":"FEBS Lett."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1128\/jvi.67.4.2091-2096.1993","article-title":"Envelope-binding domain in the cationic amino acid transporter determines the host range of ecotropic murine retroviruses","volume":"67","author":"Albritton","year":"1993","journal-title":"J. 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