{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T13:30:07Z","timestamp":1771248607293,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hungarian Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund","award":["2024-1.2.3-HU-RIZONT-2024-00062"],"award-info":[{"award-number":["2024-1.2.3-HU-RIZONT-2024-00062"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Phosphatidylinositol and its derivatives are essential components of cell membranes and play pivotal roles in growth signaling pathways. In the human primordial placenta, phosphatidylinositol synthesis is catalyzed by phosphatidylinositol synthase (PIS) and the phosphatidylinositol-exchange enzyme (IE), both of which require divalent cations. We investigated whether GTP-binding proteins modulate this biosynthetic process. Incorporation of [3H]inositol into phosphatidylinositol was measured in trophoblast tissue and microsomes from 8 to 10-week placentas. Our results demonstrate that Mn2+ strongly enhances phosphatidylinositol synthesis, and stimulation with AlF4\u2212 further increases incorporation rates by up to 2.5-fold. In contrast, Mg2+ combined with the non-hydrolyzable GTP analog GIDP elevated synthesis by 58%, whereas Mn2+ plus GIDP reduced incorporation by 30%. Complementary in silico protein\u2013protein interaction analyses suggest that G-proteins may directly associate with inositol-exchange enzymes, providing a potential mechanism for the observed regulatory effects. These findings indicate that phosphatidylinositol synthesis is modulated in a manner consistent with G-protein involvement, with distinct effects depending on the prevailing enzymatic pathway. We propose that rapid trophoblast proliferation may involve feedback mechanisms mediated by distinct G-protein subtypes acting on early steps of the phosphatidylinositol cycle.<\/jats:p>","DOI":"10.3390\/biom16020300","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T12:37:28Z","timestamp":1771245448000},"page":"300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of Phosphatidylinositol Synthesis in Human Primordial Placenta"],"prefix":"10.3390","volume":"16","author":[{"given":"Bence","family":"Kov\u00e1cs","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, \u00dcll\u0151i \u00fat 78\/a, 1082 Budapest, Hungary"},{"name":"Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, T\u0171zolt\u00f3 u. 37-47, 1093 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zolt\u00e1n","family":"Erd\u00e9lyi","sequence":"additional","affiliation":[{"name":"Institute of Pharmacogenetics, University Hospital Essen, 1085 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gergely","family":"Asb\u00f3th","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, T\u0171zolt\u00f3 u. 37-47, 1093 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e1bor","family":"Gimes","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, \u00dcll\u0151i \u00fat 78\/a, 1082 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bal\u00e1zs","family":"M\u00e9sz\u00e1ros","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, \u00dcll\u0151i \u00fat 78\/a, 1082 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zs\u00f3fia","family":"Erd\u00e9lyi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, \u00dcll\u0151i \u00fat 78\/a, 1082 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5585-2276","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Marton","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, \u00dcll\u0151i \u00fat 78\/a, 1082 Budapest, Hungary"},{"name":"Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1093 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N\u00e1ndor","family":"\u00c1cs","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, \u00dcll\u0151i \u00fat 78\/a, 1082 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorina","family":"Sup\u00e1k","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, \u00dcll\u0151i \u00fat 78\/a, 1082 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1098-1861","authenticated-orcid":false,"given":"S\u00e1ndor","family":"Valent","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, \u00dcll\u0151i \u00fat 78\/a, 1082 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zolt\u00e1n","family":"Kukor","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, T\u0171zolt\u00f3 u. 37-47, 1093 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lentini, G., Querqui, A., Giuliani, A., Verna, R., and Bizzarri, M. 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