Glutamate is the principal excitatory neurotransmitter in humans; excessive glutamate receptor signaling is responsible for much of the cell death that occurs during stroke and is also thought to play a significant role in several chronic neurodegenerative diseases. The C. elegans glutamate receptor
glr-1 has previously been described to function in the command neurons that are essential for normal locomotion 1, 2 . We have introduced an activating mutation discovered in the mouse Lurcher mutant into
glr-1 and observed a profound effect on locomotion. Transgenic worms expressing the putatively activated
glr-1 receptor have a compromised ability to translocate across a culture plate due to a five-fold increase in reversal frequency. Co-expression of a GFP reporter indicates that viability of the command neurons is not affected in this
glr-1(lurcher) strain. Since an analogous amino acid substitution in the mouse Lurcher mutant produces a constitutively activated glutamate receptor, we believe that the worm "lurching" phenotype results from constitutive depolarization of the command neurons. Villu Maricq's group at Utah has independently obtained similar results 3 . To identify prospective drug targets that would suppress glutamate receptor activity when antagonized, we have screened for recessive mutations that can suppress the lurching phenotype of activated
glr-1 . From 300,000 genomes we recovered 61 suppressed individuals in the F2 generation. Of the 42 fertile animals, 24 appeared to have defects in the integrated array as judged by loss of a co-integrated GFP marker and failure to resume lurching when outcrossed. Of the remaining isolates, 15 were independent alleles and were placed into two complementation groups. We propose the name suppressor of lurcher , or
sol-1 and
sol-2 , for these loci. 1. Maricq AV, et al., Nature. 1995 Nov 2;378(6552):78-81 2. Hart AC, et al., Nature. 1995 Nov 2;378(6552):82-5. 3. 1998 West Coast Worm Meeting abstract 79. Turning on neurons: A new genetic tool for studying neuronal circuit function in C. elegans. Yi Zheng, Penelope J. Brockie, Andres V. Maricq