Glutamate transporters have a chloride channel with two hydrophobic gates (2021) Chen et al

Colin

Established Member (Voting Rights)
Abstract:
Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and its precise control is vital to maintain normal brain function and to prevent excitotoxicity1. The removal of extracellular glutamate is achieved by plasma-membrane-bound transporters, which couple glutamate transport to sodium, potassium and pH gradients using an elevator mechanism2,3,4,5. Glutamate transporters also conduct chloride ions by means of a channel-like process that is thermodynamically uncoupled from transport6,7,8. However, the molecular mechanisms that enable these dual-function transporters to carry out two seemingly contradictory roles are unknown. Here we report the cryo-electron microscopy structure of a glutamate transporter homologue in an open-channel state, which reveals an aqueous cavity that is formed during the glutamate transport cycle. The functional properties of this cavity, combined with molecular dynamics simulations, reveal it to be an aqueous-accessible chloride permeation pathway that is gated by two hydrophobic regions and is conserved across mammalian and archaeal glutamate transporters. Our findings provide insight into the mechanism by which glutamate transporters support their dual function, and add information that will assist in mapping the complete transport cycle shared by the solute carrier 1A transporter family.

Paywall: Nature

Popular Article (with cool animation): A 'twisted elevator' could be key to understanding neurological diseases
 
Last edited:
Research like this leaves me not knowing whether to laugh or cry. There is so much still to learn about cellular function, how it works and what can go wrong with it, yet medicine screams about FND and MUS with their patronising dismissal of patients.
 

Thanks for posting this abstract.

Glutamate control / regulation is perhaps off in pwME and I hope this type of research excites ME researchers to explore and so forth, if they aren't already.

I have a paper by one of the co-authors of this paper (Ryan from 2013) detailing the mechanisms of glutamate transport. It's too big to attach. Here is the link: https://journals.physiology.org/doi/pdf/10.1152/physrev.00007.2013
 
Back
Top Bottom