{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T12:09:37Z","timestamp":1778242177339,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,5]]},"group-title":"Cell Biology","reference-count":92,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute; Division of Intramural Research","award":["ZIAHL006126"],"award-info":[{"award-number":["ZIAHL006126"]}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R35GM136265"],"award-info":[{"award-number":["R35GM136265"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["P30CA23074"],"award-info":[{"award-number":["P30CA23074"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Centrosome dysfunction is linked to developmental disorders affecting brain and body size, including microcephaly and primordial dwarfism. However, the cellular mechanisms underlying these rare conditions remain poorly understood. In this study, we investigate a rare variant of the centrosome-associated protein Pericentrin, which was discovered in a single family with Majewski\/microcephalic osteodysplastic primordial dwarfism type II (MOPD II). Unlike the majority of pathogenic\n                  <jats:italic>PCNT<\/jats:italic>\n                  variants that cause severe protein truncation, the p.Lys3154del variant (\u0394K3154) involves a single amino acid deletion in the protein\u2019s only conserved functional domain, providing a unique opportunity to explore PCNT function in MOPD II. To model\n                  <jats:italic>PCNT<\/jats:italic>\n                  <jats:sup>\u0394K3154<\/jats:sup>\n                  , we examined the effects of\n                  <jats:italic>Drosophila<\/jats:italic>\n                  Pericentrin-like protein (PLP) carrying an orthologous deletion (\n                  <jats:italic>\n                    Plp\n                    <jats:sup>\u0394R<\/jats:sup>\n                  <\/jats:italic>\n                  ). Our results show that\n                  <jats:italic>\n                    plp\n                    <jats:sup>\u0394R<\/jats:sup>\n                  <\/jats:italic>\n                  animals exhibit smaller tissues that recapitulate MOPD II phenotypes. Behavioral assays revealed defects in climbing and mechanosensation, suggesting impaired sensory cilia function. We also found that\n                  <jats:italic>\n                    Plp\n                    <jats:sup>\u0394R<\/jats:sup>\n                  <\/jats:italic>\n                  cells exhibit accelerated mitosis, increased apoptosis, and reduced pericentriolar material recruitment.\n                  <jats:italic>In silico<\/jats:italic>\n                  structural modeling, yeast two-hybrid, and co-immunoprecipitation experiments show that\n                  <jats:italic>\n                    Plp\n                    <jats:sup>\u0394R<\/jats:sup>\n                  <\/jats:italic>\n                  produces a protein that disrupts PLP dimerization and PLP interaction with Asterless, another centrosome protein. Overall, modeling the human MOPD II patient variant\n                  <jats:italic>PCNT<\/jats:italic>\n                  <jats:sup>\u0394K3154<\/jats:sup>\n                  in\n                  <jats:italic>Drosophila<\/jats:italic>\n                  reveals how a single amino acid deletion affects biological processes from the molecular level to the organismal level. Our work offers new insights into the defective cellular mechanisms underlying MOPD II in patients with the\n                  <jats:italic>PCNT<\/jats:italic>\n                  <jats:sup>\u0394K3154<\/jats:sup>\n                  variant, potentially linking the etiology of the disease in these individuals to the loss of a single protein-protein interaction.\n                <\/jats:p>","DOI":"10.64898\/2026.05.01.722250","type":"posted-content","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T21:05:27Z","timestamp":1778015127000},"source":"Crossref","is-referenced-by-count":0,"title":["A MOPD II-associated Pericentrin variant disrupts PACT domain dimerization and pericentriolar material recruitment"],"prefix":"10.64898","author":[{"given":"Makenzie S.","family":"Thomas","sequence":"first","affiliation":[{"name":"Cell and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian J.","family":"Galletta","sequence":"additional","affiliation":[{"name":"Cell and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Ryniawec","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia","family":"Amoiroglou","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaitali","family":"Khan","sequence":"additional","affiliation":[{"name":"Cell and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carey J.","family":"Fagerstrom","sequence":"additional","affiliation":[{"name":"Cell and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory C.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nasser M.","family":"Rusan","sequence":"additional","affiliation":[{"name":"Cell and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, 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