Developmental alcohol exposure impairs activity-dependent S-nitrosylation of NDEL1 for neuronal maturation

Atsushi Saito, Yu Taniguchi, Sun Hong Kim, Balakrishnan Selvakumar, Gabriel Perez, Michael D. Ballinger, Xiaolei Zhu, James Sabra, Mariama Jallow, Priscilla Yan, Koki Ito, Shreenath Rajendran, Shinji Hirotsune, Anthony Wynshaw-Boris, Solomon H. Snyder, Akira Sawa, Atsushi Kamiya

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3918-3929
Number of pages12
JournalCerebral Cortex
Issue number8
StatePublished - Aug 1 2017


  • Dendritic development
  • Fetal alcohol spectrum disorder
  • NDEL1
  • Neuronal activity
  • S-Nitrosylation

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Developmental alcohol exposure impairs activity-dependent S-nitrosylation of NDEL1 for neuronal maturation'. Together they form a unique fingerprint.

Cite this