title: Structural and Functional Consequences of Connexin 36 (Cx36) Interaction with Calmodulin.
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.
authors.affiliation: Biology Program, York University, Toronto ON, Canada.
authors.forename: Ryan C F
authors.initials: RC
authors.lastname: Siu
authors.affiliation: Chemistry Program, York University, Toronto ON, Canada.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Smirnova
authors.affiliation: Biology Program, York University, Toronto ON, Canada.
authors.forename: Cherie A
authors.initials: CA
authors.lastname: Brown
authors.affiliation: Biology Program, York University, TorontoON, Canada; Psychology Program, York University, TorontoON, Canada.
authors.forename: Christiane
authors.initials: C
authors.lastname: Zoidl
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York NY, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Spray
authors.affiliation: Biology Program, York University, Toronto ON, Canada.
authors.forename: Logan W
authors.initials: LW
authors.lastname: Donaldson
authors.affiliation: Biology Program, York University, TorontoON, Canada; Psychology Program, York University, TorontoON, Canada.
authors.forename: Georg
authors.initials: G
authors.lastname: Zoidl
keywords: CaMKII; calmodulin; connexins; electrical synapse; plasticity; protein interaction