Structural and functional consequences of connexin 36 (Cx36) interaction with calmodulin

Ryan C F Siu, Ekaterina Smirnova, Cherie A. Brown, Christiane Zoidl, David C. Spray, Logan W. Donaldson, Georg Zoidl

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Functional plasticity of neuronal gap junctions involves the interaction of the neuronal connexin36 with calcium/calmodulin-dependent kinase II (CaMKII). The important relationship between Cx36 and CaMKII must also be considered in the context of another protein partner, Ca2+ loaded calmodulin, binding an overlapping site in the carboxy-terminus of Cx36. We demonstrate that CaM and CaMKII binding to Cx36 is calcium-dependent, with Cx36 able to engage with CaM outside of the gap junction plaque. Furthermore, Ca2+ loaded calmodulin activates Cx36 channels, which is different to other connexins. The NMR solution structure demonstrates that CaM binds Cx36 in its characteristic compact state with major hydrophobic contributions arising from W277 at anchor position 1 and V284 at position 8 of Cx36. Our results establish Cx36 as a hub binding Ca2+ loaded CaM and they identify this interaction as a critical step with implications for functions preceding the initiation of CaMKII mediated plasticity at electrical synapses.

Original languageEnglish (US)
Article number120
JournalFrontiers in Molecular Neuroscience
Volume9
Issue numberNOV2016
DOIs
StatePublished - Nov 18 2016

Fingerprint

Calmodulin
Calcium-Calmodulin-Dependent Protein Kinases
Electrical Synapses
Calcium
connexin 36
Connexins
Gap Junctions
Binding Sites

Keywords

  • Calmodulin
  • CaMKII
  • Connexins
  • Electrical synapse
  • Plasticity
  • Protein interaction

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Structural and functional consequences of connexin 36 (Cx36) interaction with calmodulin. / Siu, Ryan C F; Smirnova, Ekaterina; Brown, Cherie A.; Zoidl, Christiane; Spray, David C.; Donaldson, Logan W.; Zoidl, Georg.

In: Frontiers in Molecular Neuroscience, Vol. 9, No. NOV2016, 120, 18.11.2016.

Research output: Contribution to journalArticle

Siu, Ryan C F ; Smirnova, Ekaterina ; Brown, Cherie A. ; Zoidl, Christiane ; Spray, David C. ; Donaldson, Logan W. ; Zoidl, Georg. / Structural and functional consequences of connexin 36 (Cx36) interaction with calmodulin. In: Frontiers in Molecular Neuroscience. 2016 ; Vol. 9, No. NOV2016.
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