Poster Presentation 50th Lorne Proteins Conference 2025

Characterisation of a novel C. elegans glutamate transporter homologue (#350)

Alice McCann 1 , Renae Ryan 1
  1. University of Sydney, Camperdown, NSW, Australia

Glutamate transporters are membrane bound proteins critical in the clearance of excess glutamate from the synaptic space to maintain healthy neuronal signalling and mitigate excitotoxicity. Glutamate transport occurs via a twisting-elevator mechanism which activates an uncoupled chloride conductance  linked to the pathology of neurological disorders, such as Episodic Ataxia Type 61,2,3. These dual transporter and chloride channel functions are believed to be conserved across the glutamate transporter family and havebeen characterised in human and prokaryotic homologues1. One group which remains to be characterised are glutamate transporters from the C. elegans worm; a nematode often used as a tool for investigating glutamatergic signalling. The aim of this study was to investigate the C. elegans glutamate transporter 1, or ceGlt1, using two-electrode voltage clamp (TEVC) electrophysiology. This marks the first electrophysiological characterisation of this glutamate transporter homologue in terms of substrate binding, sodium dependence and chloride conductance. The transporter shares a high sequence identity with human glutamate transporters, and previous studies indicate a high conservation of structure and function across these homologues4. Despite this, the findings of this study challenge current understanding of the conservation of the dual transport and chloride channel function of the glutamate transporter family. 

 

  1. CHEN, I., PANT, S., WU, Q., CATER, R. J., SOBTI, M., VANDENBERG, R. J., STEWART, A. G., TAJKHORSHID, E., FONT, J. & RYAN, R. M. 2021. Glutamate transporters have a chloride channel with two hydrophobic gates. Nature, 591, 327-331.
  2. JEN, J. C., WAN, J., PALOS, T. P., HOWARD, B. D. & BALOH, R. W. 2005. Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures. Neurology, 65, 529-34.
  3. WU, Q., AKHTER, A., PANT, S., CHO, E., ZHU, J. X., GARNER, A., OHYAMA, T., TAJKHORSHID, E., VAN MEYEL, D. J. & RYAN, R. M. 2022. Ataxia-linked SLC1A3 mutations alter EAAT1 chloride channel activity and glial regulation of CNS function. J Clin Invest, 132.
  4. RADICE, A. D. & LUSTIGMAN, S. 1996. Cloning and characterization of cDNAs encoding putative glutamate transporters from Caenorhabditis elegans and Onchocerca volvulus. Mol Biochem Parasitol, 80, 41- 53.