Regulation of the Ca2+/CaM-responsive pool of CaMKII by scaffold-dependent autophosphorylation.
CaMKII is critical for structural and functional plasticity. Here we show that Camguk (Cmg), the Drosophila homolog of CASK/Lin-2, associates in an ATP-regulated manner with CaMKII to catalyze formation of a pool of calcium-insensitive CaMKII. In the presence of Ca(2+)/CaM, CaMKII complexed to Cmg can autophosphorylate at T287 and become constitutively active. In the absence of Ca(2+)/CaM, ATP hydrolysis results in phosphorylation of T306 and inactivation of CaMKII. Cmg coexpression suppresses CaMKII activity in transfected cells, and the level of Cmg expression in Drosophila modulates postsynaptic T306 phosphorylation. These results suggest that Cmg, in the presence of Ca(2+)/CaM, can provide a localized source of active kinase. When Ca(2+)/CaM or synaptic activity is low, Cmg promotes inactivating autophosphorylation, producing CaMKII that requires phosphatase to reactivate. This interaction provides a mechanism by which the active postsynaptic pool of CaMKII can be controlled locally to differentiate active and inactive synapses.
Lu
Cecilia S
CS
Department of Biology and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02454, USA.
Hodge
James J L
JJ
Mehren
Jennifer
J
Sun
Xiu Xia
XX
Griffith
Leslie C
LC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006868:Hydrolysis; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D010766:Phosphorylation; D013569:Synapses / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D000255:Adenosine Triphosphate; C099190:CASK protein, Drosophila; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases