A Database of Drosophila Genes & Genomes

FB2013_03, released May 7th, 2013
 

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Citation Sun, X.X., Hodge, J.J., Zhou, Y., Nguyen, M., Griffith, L.C. (2004). The eag potassium channel binds and locally activates calcium/calmodulin-dependent protein kinase II.  J. Biol. Chem. 279(11): 10206--10214. (Export to RIS)
FlyBase ID FBrf0174770
Publication Type Research paper
PubMed ID 14699099
PubMed Abstract Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the regulation of neuronal excitability in many systems. Recent studies suggest that local regulation of membrane potential can have important computational consequences for neuronal function. In Drosophila, CaMKII regulates the eag potassium channel, but if and how this regulation was spatially restricted was unknown. Using coimmunoprecipitation from head extracts and in vitro binding assays, we show that CaMKII and Eag form a stable complex and that association with Eag activates CaMKII independently of CaM and autophosphorylation. Ca(2+)/CaM is necessary to initiate binding of CaMKII to Eag but not to sustain association because binding persists when CaM is removed. The Eag CaMKII-binding domain has homology to the CaMKII autoregulatory region, and the constitutively active CaMKII mutant, T287D, binds Eag Ca(2+)-independently in vitro and in vivo. These results favor a model in which the CaMKII-binding domain of Eag displaces the CaMKII autoinhibitory region. Displacement results in autophosphorylation-independent activation of CaMKII which persists even when Ca(2+) levels have gone down. Activity-dependent binding to this potassium channel substrate allows CaMKII to remain locally active even when Ca(2+) levels have dropped, providing a novel mechanism by which CaMKII can regulate excitability locally over long time scales.
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Language of Publication English
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Publication Type Journal
Abbreviation J. Biol. Chem.
Title Journal of Biological Chemistry
Publication Year 1905-
ISBN/ISSN 0021-9258
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