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One such gene, tryptophan\u2010aspartate repeat domain 72\u00a0(<jats:italic>WDR72<\/jats:italic>), has been found to cause\u00a0a tooth enamel defect when deleted or mutated, resulting in a condition called amelogenesis imperfecta. Unlike the canonical genes regulating tooth development, WDR72 remains intracellularly and is not secreted to the enamel matrix space to regulate mineralization, and is found in other major organs of the body, namely the kidney, brain, liver, and heart. To date, a link between intracellular vesicle transport and enamel mineralization has been suggested, however identification of the mechanistic regulators has yet to be elucidated, in part due to the limitations associated with studying highly differentiated ameloblast cells. Here we show compelling evidence that WDR72 regulates endocytosis of proteins, both\u00a0in vivo\u00a0and in a novel\u00a0in vitro\u00a0ameloblast cell line<jats:italic>.<\/jats:italic>\u00a0We elucidate WDR72\u2019s function to be independent of\u00a0<jats:italic>intracellular<\/jats:italic>\u00a0vesicle acidification while still leading to defective enamel matrix pH\u00a0<jats:italic>extracellularly.<\/jats:italic>\u00a0We identify a vesicle function associated with microtubule assembly and propose that WDR72 directs microtubule assembly necessary for membrane mobilization and subsequent vesicle transport. Understanding WDR72 function provides a mechanistic basis for determining physiologic and pathologic tissue mineralization.<\/jats:p>","DOI":"10.1038\/s41598-022-06751-1","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T11:24:46Z","timestamp":1645183486000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["WDR72 regulates vesicle trafficking in ameloblasts"],"prefix":"10.1038","volume":"12","author":[{"given":"Kaitlin","family":"Katsura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rozana","family":"Shemirani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Den Besten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"6751_CR1","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1159\/000322036","volume":"194","author":"W El-Sayed","year":"2011","unstructured":"El-Sayed, W., Shore, R. 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