Caenorhabditis elegans Glutamate Transporters Influence Synaptic Function and Behavior at Sites Distant from the Synapse

Abstract

To ensure precise neurotransmission and prevent neurotoxic accumulation, l-glutamate (Glu), the major excitatory neurotransmitter in the brain, is cleared from the synapse by glutamate transporters (GluTs). The molecular components of Glu synapses are highly conserved between Caenorhabditis elegans and mammals, yet the absence of synaptic insulation in C. elegans raises fundamental questions about Glu clearance strategies in the nematode nervous system. To gain insight into how Glu clearance is accomplished and how GluTs impact neurotransmission, we probed expression and function of all 6 GluTs found in the C. elegans genome. Disruption of each GluT impacts multiple Glu-dependent behaviors, with GluT combinations commonly increasing the severity of behavioral deficits. Interestingly, the sole GluT we in is in in the of GluTs in of the 6 GluT the Glu-dependent from of of the function the by synaptic and synaptic The of GluTs Glu the of the synapse is in C. elegans with the of Glu clearance in C. To ensure precise neurotransmission and prevent neurotoxic accumulation, l-glutamate (Glu), the major excitatory neurotransmitter in the brain, is cleared from the synapse by glutamate transporters (GluTs). The molecular components of Glu synapses are highly conserved between Caenorhabditis elegans and mammals, yet the absence of synaptic insulation in C. elegans raises fundamental questions about Glu clearance strategies in the nematode nervous system. To gain insight into how Glu clearance is accomplished and how GluTs impact neurotransmission, we probed expression and function of all 6 GluTs found in the C. elegans genome. Disruption of each GluT impacts multiple Glu-dependent behaviors, with GluT combinations commonly increasing the severity of behavioral deficits. Interestingly, the sole GluT we in is in in the of GluTs in of the 6 GluT the Glu-dependent from of of the function the by synaptic and synaptic The of GluTs Glu the of the synapse is in C. elegans with the of Glu clearance in C. glutamate glutamate glutamate glutamate glutamate glutamate is the neurotransmitter excitatory in the and in in and synaptic Glu by is in of To Glu and the synapse in the Glu in synapses synaptic is from the by Glu transporters mammals, Glu clearance is accomplished by GluTs the of the synapse with by transporters are neurotransmission in Caenorhabditis with conserved and of into of neurotransmitter synaptic and in of neurotransmission are in C. and the molecular components of Glu synapses are highly conserved between C. elegans and Glu transporters of are found in the and of and Glu C. elegans all C. elegans and are in synapses excitatory the by Glu and in the conserved excitatory Glu Glu in C. elegans by the of the by is about Glu clearance in C. molecular of nematode GluT and in the molecular components of GluTs are and conserved between and the of in C. elegans from the of the molecular of Glu and the of synapses and behaviors, major in of neurotransmission in The of the nematode nervous in synaptic are by insulation by raises questions the the of neurotransmission in C. elegans and the of Glu clearance in we the expression and the of all 6 GluT by the C. elegans of Glu clearance in the function of GluT in how nematode from the in C. elegans is Glu clearance is in of synaptic C. elegans from the C. elegans from and the The GluT from from the C. elegans and from the the nematode of of C. elegans of and of The by the is of and with the are in in we in in in the and 6 each in GluT multiple and the combinations by the of with with by with of and behavioral is the C. elegans 6 with Glu C. elegans 6 GluT and from of and is Glu in The found in the are 6 nematode GluTs of GluTs is in of the of GluTs all 6 C. elegans GluTs the with the of the 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