TY - JOUR
T1 - Developmental alcohol exposure impairs activity-dependent S-nitrosylation of NDEL1 for neuronal maturation
AU - Saito, Atsushi
AU - Taniguchi, Yu
AU - Kim, Sun Hong
AU - Selvakumar, Balakrishnan
AU - Perez, Gabriel
AU - Ballinger, Michael D.
AU - Zhu, Xiaolei
AU - Sabra, James
AU - Jallow, Mariama
AU - Yan, Priscilla
AU - Ito, Koki
AU - Rajendran, Shreenath
AU - Hirotsune, Shinji
AU - Wynshaw-Boris, Anthony
AU - Snyder, Solomon H.
AU - Sawa, Akira
AU - Kamiya, Atsushi
N1 - Publisher Copyright:
© The Author 2016. Published by Oxford University Press. All rights reserved.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Neuronal nitric oxide synthase is involved in diverse signaling cascades that regulate neuronal development and functions via S-Nitrosylation-mediated mechanism or the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway activated by nitric oxide. Although it has been studied extensively in vitro and in invertebrate animals, effects on mammalian brain development and underlying mechanisms remain poorly understood. Here we report that genetic deletion of "Nos1" disrupts dendritic development, whereas pharmacological inhibition of the sGC/cGMP pathway does not alter dendritic growth during cerebral cortex development. Instead, nuclear distribution element-like (NDEL1), a protein that regulates dendritic development, is specifically S-nitrosylated at cysteine 203, thereby accelerating dendritic arborization. This post-translational modification is enhanced by N-methyl-D-aspartate receptor-mediated neuronal activity, the main regulator of dendritic formation. Notably, we found that disruption of S-Nitrosylation of NDEL1 mediates impaired dendritic maturation caused by developmental alcohol exposure, a model of developmental brain abnormalities resulting from maternal alcohol use. These results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure.
AB - Neuronal nitric oxide synthase is involved in diverse signaling cascades that regulate neuronal development and functions via S-Nitrosylation-mediated mechanism or the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway activated by nitric oxide. Although it has been studied extensively in vitro and in invertebrate animals, effects on mammalian brain development and underlying mechanisms remain poorly understood. Here we report that genetic deletion of "Nos1" disrupts dendritic development, whereas pharmacological inhibition of the sGC/cGMP pathway does not alter dendritic growth during cerebral cortex development. Instead, nuclear distribution element-like (NDEL1), a protein that regulates dendritic development, is specifically S-nitrosylated at cysteine 203, thereby accelerating dendritic arborization. This post-translational modification is enhanced by N-methyl-D-aspartate receptor-mediated neuronal activity, the main regulator of dendritic formation. Notably, we found that disruption of S-Nitrosylation of NDEL1 mediates impaired dendritic maturation caused by developmental alcohol exposure, a model of developmental brain abnormalities resulting from maternal alcohol use. These results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure.
KW - Dendritic development
KW - Fetal alcohol spectrum disorder
KW - NDEL1
KW - Neuronal activity
KW - S-Nitrosylation
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U2 - 10.1093/cercor/bhw201
DO - 10.1093/cercor/bhw201
M3 - Article
C2 - 27371763
AN - SCOPUS:85026558223
SN - 1047-3211
VL - 27
SP - 3918
EP - 3929
JO - Cerebral Cortex
JF - Cerebral Cortex
IS - 8
ER -