Calcium/Calmodulin-dependent Protein Kinase II
Phosphorylates and Regulates the Drosophila Eag Potassium
Channel*
Zheng
Wang
§,
Gisela F.
Wilson¶, and
Leslie C.
Griffith
From the Department of Biology and Volen Center for
Complex Systems, Brandeis University, Waltham, Massachusetts 02454-9110 and the ¶ Department of Molecular, Cellular, and Developmental
Biology, University of Michigan,
Ann Arbor, Michigan 48109
Modulation of neuronal excitability is believed
to be an important mechanism of plasticity in the nervous system.
Calcium/calmodulin-dependent protein kinase II (CaMKII) has
been postulated to regulate the ether à go-go
(eag) potassium channel in Drosophila.
Inhibition of CaMKII and mutation of the eag gene both
cause hyperexcitability at the larval neuromuscular junction (NMJ) and
memory formation defects in the adult. In this study, we identify a
single site, threonine 787, as the major CaMKII phosphorylation site in
Eag. This site can be phosphorylated by CaMKII both in a heterologous cell system and in vivo at the larval NMJ. Expression of
Eag in Xenopus oocytes was used to assess the function of
phosphorylation. Injection of either a specific CaMKII inhibitor
peptide or lavendustin C, another CaMKII inhibitor, reduced Eag current
amplitude acutely. Mutation of threonine 787 to alanine also reduced
amplitude. Moreover, both CaMKII inhibition and the alanine mutation
accelerated inactivation. The reduction in current amplitudes and the
accelerated inactivation of dephosphorylated Eag channels would result
in decreased outward potassium currents and hyperexcitability at
presynaptic terminals and, thus, are consistent with the NMJ
phenotype observed when CaMKII is inhibited. These results show that
Eag is a substrate of CaMKII and suggest that direct modulation of
potassium channels may be an important function of this kinase.
*
This work was supported by National Institutes of Health
Grants GM54408 (to L. C. G.) and MH62648 (to G. F. W.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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