Coordination between calcium/calmodulin-dependent protein kinase II and neuronal nitric oxide synthase in neurons

Shoma Araki, Koji Osuka, Tsuyoshi Takata, Yukihiro Tsuchiya, Yasuo Watanabe

Research output: Contribution to journalReview articlepeer-review

12 Citations (Scopus)


Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) is highly abundant in the brain and exhibits broad substrate specificity, thereby it is thought to participate in the regulation of neuronal death and survival. Nitric oxide (NO), produced by neuronal NO synthase (nNOS), is an important neurotransmitter and plays a role in neuronal activity including learning and memory processes. However, high levels of NO can contribute to excitotoxicity following a stroke and neurodegenerative disease. Aside from NO, nNOS also generates superoxide which is involved in both cell injury and signaling. CaMKII is known to activate and translocate from the cytoplasm to the post-synaptic density in response to neuronal activation where nNOS is predominantly located. Phosphorylation of nNOS at Ser847 by CaMKII decreases NO generation and increases superoxide generation. Conversely, NO-induced S-nitrosylation of CaMKII at Cys6 is a prominent determinant of the CaMKII inhibition in ATP competitive fashion. Thus, the ‘cross-talk’ between CaMKII and NO/superoxide may represent important signal transduction pathways in brain. In this review, we introduce the molecular mechanism of and pathophysiological role of mutual regulation between CaMKII and nNOS in neurons.

Original languageEnglish
Article number7997
Pages (from-to)1-17
Number of pages17
JournalInternational journal of molecular sciences
Issue number21
Publication statusPublished - 2020 Nov 1


  • Ca2+/calmodulin-dependent protein kinase II (CaMKII)
  • Neuronal ischemia
  • Nitric-oxide (NO)
  • Phosphorylation
  • Redox regulation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


Dive into the research topics of 'Coordination between calcium/calmodulin-dependent protein kinase II and neuronal nitric oxide synthase in neurons'. Together they form a unique fingerprint.

Cite this