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dc.contributor.authorYang, P.
dc.contributor.authorXu, C.
dc.contributor.authorReece, E.A.
dc.date.accessioned2019-03-29T14:47:33Z
dc.date.available2019-03-29T14:47:33Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85060149339&doi=10.1038%2fs41467-018-08268-6&partnerID=40&md5=1060d6b8b72ba62476ced0d97c99db23
dc.identifier.urihttp://hdl.handle.net/10713/8641
dc.description.abstractFailure of neural tube closure results in severe birth defects and can be induced by high glucose levels resulting from maternal diabetes. MARCKS is required for neural tube closure, but the regulation and of its biological activity and function have remained elusive. Here, we show that high maternal glucose induced MARCKS acetylation at lysine 165 by the acetyltransferase Tip60, which is a prerequisite for its phosphorylation, whereas Sirtuin 2 (SIRT2) deacetylated MARCKS. Phosphorylated MARCKS dissociates from organelles, leading to mitochondrial abnormalities and endoplasmic reticulum stress. Phosphorylation dead MARCKS (PD-MARCKS) reversed maternal diabetes-induced cellular organelle stress, apoptosis and delayed neurogenesis in the neuroepithelium and ameliorated neural tube defects. Restoring SIRT2 expression in the developing neuroepithelium exerted identical effects as those of PD-MARCKS. Our studies reveal a new regulatory mechanism for MARCKS acetylation and phosphorylation that disrupts neurulation under diabetic conditions by diminishing the cellular organelle protective effect of MARCKS. ©2019, The Author(s).en_US
dc.description.urihttps://dx.doi.org/10.1038/s41467-018-08268-6en_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofNature Communications
dc.subject.meshNeural Tube Defectsen_US
dc.subject.meshMyristoylated Alanine-Rich C Kinase Substrateen_US
dc.titleTip60- and sirtuin 2-regulated MARCKS acetylation and phosphorylation are required for diabetic embryopathyen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41467-018-08268-6
dc.identifier.pmid30655546


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