[
International C. elegans Meeting,
1999]
Glutamate (Glu) is the major excitatory neurotransmitter in the mammalian brain. Glu is involved in a wide spectrum of developmental, physiological and pathological processes. Glu exerts these activities by activating ionotropic and metabotropic receptors (GluRs) that assemble via PDZ-domain containing proteins into complexes with other membrane and cytoplasmic proteins that modulate the specific signal. A central determinant of Glu action is its rate of removal from the synaptic cleft, mediated by specific Glu transporters (GluTs). Molecular analysis in C. elegans and physiological analysis in A. suum suggest that many of the molecules and functional aspects of glutamatergic neurotransmission are conserved from nematodes to humans. The C. elegans genome includes six genes that are highly homologous to mammalian GluTs. In order to gain insight into the mechanisms of normal and abnormal glutamatergic neurotransmission in the worm, we are conducting systematic screens of deletion libraries for strains harboring knockouts of worm GluTs. We have isolated a knockout of the K08F4.4 GluT gene and we are currently characterizing its phenotype. We are screening additional libraries to isolate knockouts in the other worm GluTs. We plan to determine expression patterns and RNAi phenotypes of all worm GluTs. Our long-term goal in elaborating phenotypes of GluT knockouts is to elucidate the mechanisms of action of known and novel gene products that participate in normal and pathological processes induced by Glutamatergic neurotransmission.