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Publication : Folate-dependent methylation of septins governs ciliogenesis during neural tube closure.

First Author  Toriyama M Year  2017
Journal  FASEB J Volume  31
Issue  8 Pages  3622-3635
PubMed ID  28432198 Mgi Jnum  J:252686
Mgi Id  MGI:5927336 Doi  10.1096/fj.201700092R
Citation  Toriyama M, et al. (2017) Folate-dependent methylation of septins governs ciliogenesis during neural tube closure. FASEB J 31(8):3622-3635
abstractText  Periconception maternal folic acid (vitamin B9) supplementation can reduce the prevalence of neural tube defects (NTDs), although just how folates benefit the developing embryo and promote closing of the neural tube and other morphologic processes during development remains unknown. Folate contributes to a 1-carbon metabolism, which is essential for purine biosynthesis and methionine recycling and affects methylation of DNA, histones, and nonhistone proteins. Herein, we used animal models and cultured mammalian cells to demonstrate that disruption of the methylation pathway mediated by folate compromises normal neural tube closure (NTC) and ciliogenesis. We demonstrate that the embryos with NTD failed to adequately methylate septin2, a key regulator of cilium structure and function. We report that methylation of septin2 affected its GTP binding activity and formation of the septin2-6-7 complex. We propose that folic acid promotes normal NTC in some embryos by regulating the methylation of septin2, which is critical for normal cilium formation during early embryonic development.-Toriyama, M., Toriyama, M., Wallingford, J. B., Finnell, R. H. Folate-dependent methylation of septins governs ciliogenesis during neural tube closure.
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