High impact information on eag

• Together with DNA sequence analysis, the results suggest that the eag locus encodes a subunit common to different potassium channels [1].
• In voltage-clamped larval muscle fibers, Sh affects the transient A current, whereas Eag reduces the delayed rectification and, to a lesser extent, the A current [2].
• Electrophysiological analysis of the Drosophila behavioral mutants Eag and Sh and the double mutant Eag Sh indicates that the products of both genes take part in the control of potassium currents in the membranes of both nerve and muscle [2].
• Increased neuronal activity (eag Shaker mutants) and cAMP concentration (dunce mutants) lead to increased synaptic structure and function at the Drosophila neuromuscular junction [3].
• This decrease in Fas II is both necessary and sufficient for presynaptic sprouting; FasII mutants that decrease Fas II levels by approximately 50% lead to sprouting similar to eag Shaker and dunce, while transgenes that maintain synaptic Fas II levels suppress sprouting in eag Shaker and dunce [3].

Biological context of eag

• Similar to eag Sh double mutants, double mutants of eag and qvr(1) showed striking enhancement in synaptic transmission and a wings-down phenotype, the hallmarks of extreme hyperexcitability [4].
• We used recombination mapping to localize both mutations to the eag locus, and we used sequence analysis to determine that both mutations are caused by a single amino acid substitution (G297E) in the S2-S3 linker of Eag [5].
• Two mutants, eag (ether à go-go) and Sh (Shaker), are known to increase excitability of both nerve and muscle cells and enhance synaptic transmission by affecting different types of K+ currents [6].
• A genomic library was prepared from In(1)sc29 and screened with a genomic DNA fragment that spanned the sc breakpoint to isolate DNA from the eag region [7].
• Expression of Eag in Xenopus oocytes was used to assess the function of phosphorylation [8].

Anatomical context of eag

• 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 [8].
• These functional abnormalities are similar to those found in other hyperexcitable mutants (Shaker, ether-a-gogo, Hyperkinetic) which, in turn, exhibit increased branching at the motor nerve endings [9].
• Mutations of eag, first identified in Drosophila on the basis of their leg-shaking phenotype, cause repetitive firing and enhanced transmitter release in motor neurons [10].

Associations of eag with chemical compounds

• Heterologously expressed Hk dramatically increases the amplitudes of eag currents and also affects gating and modulation by progesterone [11].
• Moreover, independent of inactivation, repositioning of the equivalent aromatic residues in Drosophila eag channels induced sensitivity to block by cisapride [12].
• In this study, we identify a single site, threonine 787, as the major CaMKII phosphorylation site in Eag [8].
• Injection of either a specific CaMKII inhibitor peptide or lavendustin C, another CaMKII inhibitor, reduced Eag current amplitude acutely [8].
• To exert its effect, Mg(2+) presumably binds to a site in or near the eag voltage sensor [13].

Physical interactions of eag

• These results favor a model in which the CaMKII-binding domain of Eag displaces the CaMKII autoinhibitory region [14].

Enzymatic interactions of eag

• Calcium/calmodulin-dependent protein kinase II phosphorylates and regulates the Drosophila eag potassium channel [8].

Regulatory relationships of eag

• In Drosophila, CaMKII regulates the eag potassium channel, but if and how this regulation was spatially restricted was unknown [14].
• The eag potassium channel binds and locally activates calcium/calmodulin-dependent protein kinase II [14].

Other interactions of eag

• We found that Sh, Hk, and eag mutant flies were all hypersensitive to paraquat [4].
• However, in combinations of eag and Sh alleles, the basic pattern of innervation was altered [15].
• This abnormal pattern of activity could be partially suppressed by napts in combination with eag Sh [15].
• Furthermore, Khc: mutations suppress Shaker and ether-a-go-go mutations that disrupt potassium channel activity [16].
• Neither eag (0.66), para (0.48), nor slo (0.63) differed significantly from the wild type [17].

Analytical, diagnostic and therapeutic context of eag

• Three additional eag alleles, including two dysgenesis-induced insertion mutations and a gamma-ray-induced insertional translocation, were located on the molecular map of the eag locus by Southern blot analysis [7].
• Complementation tests showed that it is allelic to eag [18].

References