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Comments on Qiang Liu et al. (2007) International Worm Meeting "Presynaptic CaMKII Modulates Neurotransmitter Release by Activating BK Channels at C. elegans Neuromuscular Junction." (0)
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Qiang Liu, Bojun Chen, Qian Ge, & Zhao-Wen Wang (2007). Presynaptic CaMKII Modulates Neurotransmitter Release by Activating BK Channels at C. elegans Neuromuscular Junction presented in International Worm Meeting. Unpublished information; cite only with author permission.
CaMKII plays key roles in controlling synaptic strength and plasticity. Although the function of postsynaptic CaMKII is well-known, that of presynaptic CaMKII is poorly defined. To understand the function of presynaptic CaMKII, it is important to identify its molecular targets. We assessed the function of presynaptic CaMKII in neurotransmitter release and the possibility of the BK channel as a mediator of presynaptic CaMKII function by analyzing miniature and evoked postsynaptic currents at the C. elegans neuromuscular junction. The BK channel was chosen as a candidate because (1) it plays a major role in regulating neurotransmitter release, (2) it may be activated by CaMKII, and (3) loss-of-function mutants of both unc-43 CaMKII and slo-1 BK channel were isolated in the same genetic screen as suppressors of the lethargic phenotype of a hypomorphic unc-64 syntaxin mutant (Wang et al., 2001). We found that either loss-of-function (lf) or gain-of-function (gf) of unc-43 inhibited neurotransmitter release. The inhibitory effect of unc-43(gf) was reversed by mutation or blockade of SLO-1. SLO-1 expressed in Xenopus oocytes could be activated by recombinant rat <font face=symbol>a</font>-CaMKII, and this effect of CaMKII was abolished by mutating a threonine residue (T425) at a consensus CaMKII phosphorylation site in the first RCK domain (regulator of conductance for K+) of the channel. The inhibitory effect of unc-43(gf) was not reversed by unc-103(lf), dgk-1(lf), or eat-16(lf), which may suppress behavioral phenotypes of unc-43(gf) (Robatzek and Thomas, 2000). These observations suggest that presynaptic CaMKII is a bidirectional modulator of neurotransmitter release, presumably by phosphorylating different molecular targets, and that its negative modulatory effect on the release is mainly mediated by SLO-1 activation.