title: Calcium/Calmodulin-dependent protein kinase is negatively and positively regulated by calcium, providing a mechanism for decoding calcium responses during symbiosis signaling.
abstract: The establishment of symbiotic associations in plants requires calcium oscillations that must be decoded to invoke downstream developmental programs. In animal systems, comparable calcium oscillations are decoded by calmodulin (CaM)-dependent protein kinases, but symbiotic signaling involves a calcium/CaM-dependent protein kinase (CCaMK) that is unique to plants. CCaMK differs from the animal CaM kinases by its dual ability to bind free calcium, via calcium binding EF-hand domains on the protein, or to bind calcium complexed with CaM, via a CaM binding domain. In this study, we dissect this dual regulation of CCaMK by calcium. We find that calcium binding to the EF-hand domains promotes autophosphorylation, which negatively regulates CCaMK by stabilizing the inactive state of the protein. By contrast, calcium-dependent CaM binding overrides the effects of autophosphorylation and activates the protein. The differential calcium binding affinities of the EF-hand domains compared with those of CaM suggest that CCaMK is maintained in the inactive state at basal calcium concentrations and is activated via CaM binding during calcium oscillations. This work provides a model for decoding calcium oscillations that uses differential calcium binding affinities to create a robust molecular switch that is responsive to calcium concentrations associated with both the basal state and with oscillations.
authors.affiliation: John Ines Centre, Norwich NR4 7UH, United Kingdom.
authors.forename: J Benjamin
authors.initials: JB
authors.lastname: Miller
authors.forename: Amitesh
authors.initials: A
authors.lastname: Pratap
authors.forename: Akira
authors.initials: A
authors.lastname: Miyahara
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.forename: Stephen
authors.initials: S
authors.lastname: Bornemann
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Morris
authors.forename: Giles E D
authors.initials: GE
authors.lastname: Oldroyd
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D046913:Medicago truncatula / Q000378:metabolism* / Q000382:microbiology; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D016962:Sinorhizobium meliloti / Q000378:metabolism*; D013559:Symbiosis
chemical_list: D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium