33 ± 23.07 pA, n = 6) ( Figure 4D). These results indicate that the binding of exogenously delivered s-SOL-1 is sufficient to reconstitute the function of the receptor complex and that SOL-2 is required cell autonomously to recruit s-SOL-1 to the complex. Our results also suggest that in sol-1 mutants the remaining components of the receptor complex are stably located in the plasma membrane. Presumably, muscle-secreted s-SOL-1 diffuses in the extracellular space and binds to neuronal SOL-2 to reconstitute the GLR-1 receptor complex. One might imagine that postsynaptic signaling molecules, such as SOL-1, have critical developmental roles in addition

to their known signaling functions. Thus, the behavioral defects in sol-1 mutants might also be a consequence of developmental defects in synaptic morphology or function. To test whether SOL-1 has an obligate developmental role, we generated transgenic sol-1; lurcher Selisistat and sol-1; sol-2; lurcher mutants that expressed GFP::s-SOL-1 under the control of a heat-shock HIF pathway inducible promoter (Phsp::gfp::s-sol-1). Four hours following heat shock of adult worms, we assessed their behavior. In the absence of the Phsp::gfp::s-sol-1 transgene, or in the absence of heat shock, sol-1; lurcher mutants did not reverse nearly as often as wild-type lurcher worms ( Figure 4E). In contrast, heat shock induction of GFP::s-SOL-1 rescued reversal

behavior in adult sol-1; lurcher mutants, and the rescue was dependent on sol-2 ( Figure 4E). In a complementary set of experiments, we examined whether heat shock driven expression of SOL-2::GFP in adult sol-2 mutants could similarly rescue the behavioral phenotype. Following heat shock induction, reversal behavior in adult sol-2; lurcher mutants was restored to wild-type values ( Figure 4F).

We extended these studies to examine glutamate-gated currents in heat-shocked worms and next found that within 4 hr of heat shock we could record near wild-type glutamate-gated currents from the transgenic sol-2 mutants ( Figure 4G). These experiments demonstrate that the function of s-SOL-1 is dependent on SOL-2, that the remaining components of the receptor signaling complex are stable in the absence of SOL-1, and that SOL-1 and SOL-2 have ongoing roles in synaptic transmission in the adult nervous system. Glutamate-gated currents are significantly reduced in sol-2 mutants, yet paradoxically, SOL-2 is not essential for reconstitution studies in muscle cells or Xenopus oocytes ( Figure 1; Walker et al., 2006a, 2006b). One possibility is that the overexpression of SOL-1 in reconstitution studies partially compensates for the absence of SOL-2. This hypothesis predicts that overexpressing SOL-1 in sol-2 mutants should rescue glutamate-gated currents. Conversely, overexpressing SOL-2 should not rescue sol-1 mutants.