Go Directly (or Indirectly) to Gq

1999). However, egl-30 G q ␣ probably has additional ef-(or Indirectly) to Gq fectors, since a presumptive loss-of-function allele of egl-8 PLC␤ causes less severe phenotypes than strong reduction-of-function alleles of egl-30 G q ␣ (Miller et al., 1999). A fundamental mechanism for regulating synaptic trans-Since diacylglycerol (DAG) is a major end product mission is the control of neurotransmitter secretion by of the G q ␣–PLC␤ pathway in vertebrates, both groups presynaptic neurons. Recent papers, including two in asked whether DAG can positively regulate ACh release this issue of Neuron (Lackner et al., 1999; Miller et al., in C. elegans. Treatment of worms with phorbol esters, 1999), indicate that a hierarchical network of G proteins analogs of DAG, increased sensitivity to aldicarb, indi-controls, among other things, release of the neurotrans-cating that DAG positively regulates synaptic transmis-mitter acetylcholine (ACh) at the neuromuscular junction sion. Lackner et al. (1999) additionally show that treat-in C. elegans. In this organism, ventral cord motor neu-ment with phorbol esters restores aldicarb sensitivity to rons use ACh to stimulate contraction of body wall mus-egl-30 G q ␣ and egl-8 PLC␤ mutants, as is expected if cles. This stimulation, alternating with a coordinated these genes normally function to produce DAG. This relaxation program, results in the typical sinusoidal move-group also demonstrates that one target of DAG is UNC-ment of nematodes (Herman, 1993; Rand and Nonet, 13, a presynaptic DAG-binding protein, although there 1997). is evidence that UNC-13 is not the only target responsi-Mutations in two G protein ␣ subunit genes, goa-1 ble for the stimulation of ACh release by the egl-30 G q ␣ G o ␣ and egl-30 G q ␣, cause opposite effects on nematode pathway. The figure diagrams the relationship among movement. Loss-of-function mutations in goa-1 cause these molecules. Muscarinic agonists such as arecoline hyperactive movement, while reduction-of-function al-activate egl-30 G q ␣, which in turn activates egl-8 PLC␤. leles of egl-30 result in lethargy. Overexpression of wild-Activated egl-8 PLC␤ cleaves phosphatidylinositol 4,5-type or constitutively activated transgenes for each G␣ bisphosphate (PIP 2) into DAG and inositol 1,4,5-tris-subunit also results in opposite phenotypes: too much phosphate (IP 3 ; not shown). DAG stimulates ACh release G o ␣ activity makes worms lethargic, whereas too much through UNC-13 and possibly other molecules. EGL-30 G q ␣ activity makes them hyperactive (Mendel et al. The papers presented here provide insight into the The G protein pathway involving …