Robatzek M, Thomas J H
Department of Genetics, University of Washington, Seattle, Washington 98195, USA.
Genetics. 2000 Nov;156(3):1069-82. doi: 10.1093/genetics/156.3.1069.
Caenorhabditis elegans locomotion is a complex behavior generated by a defined set of motor neurons and interneurons. Genetic analysis shows that UNC-43, the C. elegans Ca(2+)/calmodulin protein kinase II (CaMKII), controls locomotion rate. Elevated UNC-43 activity, from a gain-of-function mutation, causes severely lethargic locomotion, presumably by inappropriate phosphorylation of targets. In a genetic screen for suppressors of this phenotype, we identified multiple alleles of four genes in a G(o)/G(q) G-protein signaling network, which has been shown to regulate synaptic activity via diacylglycerol. Mutations in goa-1, dgk-1, eat-16, or eat-11 strongly or completely suppressed unc-43(gf) lethargy, but affected other mutants with reduced locomotion only weakly. We conclude that CaMKII and G(o)/G(q) pathways act in concert to regulate synaptic activity, perhaps through a direct interaction between CaMKII and G(o).
秀丽隐杆线虫的运动是一种由一组特定的运动神经元和中间神经元产生的复杂行为。遗传分析表明，线虫的钙/钙调蛋白依赖性蛋白激酶II（CaMKII）UNC-43控制运动速度。功能获得性突变导致UNC-43活性升高，可能通过对靶点的不适当磷酸化导致严重的运动迟缓。在对该表型抑制子的遗传筛选中，我们在一个G(o)/G(q) G蛋白信号网络中鉴定出四个基因的多个等位基因，该网络已被证明可通过二酰甘油调节突触活性。goa-1、dgk-1、eat-16或eat-11中的突变强烈或完全抑制unc-43(gf)的运动迟缓，但对其他运动减少的突变体影响较弱。我们得出结论，CaMKII和G(o)/G(q)途径协同作用以调节突触活性，可能是通过CaMKII与G(o)之间的直接相互作用。
