Ion channel modulation can influence and alter synaptic transmission, thereby affecting information processing at the nervous system. Slob is a novel binding partner that influences the activity and subcellular localization of the Drosophila Slowpoke (dSlo) calcium-dependent potassium channel. The ubiquitous signaling protein scaffold, 14-3-3, binds to and modulates dSlo, via Slob. Two phosphorylatable serine residues in Slob are required for the binding of and modulation by 14-3-3. All three of these proteins are co-localized in an immunoprecipitating complex in Drosophila presynaptic nerve terminals. Because 14-3-3 has been shown to be important for transmitter release (Davis et al., 1997), we propose to test the role of this signaling complex in the regulation of synaptic transmission at the neuromuscular junction. We will examine transgenic flies that overexpress a double-serine mutant Slob that can bind to dSlo but not to 14-3-3, hence acting as a dominant negative. Information in the nervous system is determined by the frequency and variation of the firing pattern of neuronal synapses. dSlo contributes to membrane repolarization and the level of excitability of the neuron, it is conceivable that altering these features by Slob and 14-3-3 may affect information processing in the nervous system. Any modulator that influences the opening of a potassium channel can alter excitability of the cells expressing the channel, and thus may reveal some potential therapeutic application.
