Genetic studies suggest that the integrated activities of at least 3 major G alpha pathways control synaptic activity to produce the C. elegans locomotion behavior. In this network, a core EGL-30 (Gq) pathway drives locomotion by a mechanism that is dependent on the UNC-13 synaptic vesicle priming protein. UNC-31, a dense-core vesicle priming protein, is required for activation of a functionally distinct but interacting neuronal Gs pathway, which drives locomotion by a mechanism that is dependent on the Gq pathway. Strong reduction-of-function mutants in the Gq pathway or UNC-13, and null mutants in UNC-31 or the neuronal Gs pathway are nearly paralyzed, with locomotion rates ~1 - 3% of wild type. We recently made the startling observation that blue light causes both wild type and
unc-31 null mutants to begin moving hyperactively in a coordinated manner. Using different filters and light equipment to control and measure the light fluence, we found that the action spectrum peaks in the UV range, and that worms are unresponsive to green and orange light, even at very high fluence. The response is not caused by small temperature changes induced by the light, since green light causes a greater temperature change than blue-violet light of the same power. The response is photophobic, originates in the nerve cords, begins within 1-2 sec (for wild type), and is saturable. Bathing paralyzed
egl-30(
ad805) mutants in optimal light restores coordinated wild type locomotion but doesn"t make them hyperactive as is the case for
unc-31 and neuronal Gs pathway nulls. In contrast, similarly paralyzed
unc-13 mutants are unresponsive to light. Our results suggest that high energy light activates a pathway that plugs into a downstream component of the synaptic signaling network and affects a process that is dependent on UNC-13. To investigate the mechanism of this response, we carried out a large forward genetic screen for mutants that are unresponsive to high energy light but have near-wild type sensitivity to physical stimuli. We found 19 Lite mutants, representing 1 principal target (
lite-1) and 1 or more rare targets. We have mapped
lite-1 to a physical interval and are testing candidate genes for
lite-1 mutations.