What is it about?

Within the superfamily of glutamate receptors that mediate excitatory signals between nerve cells, one particular type - delta - appears strangely inacitve in vertebrates. By characterizing delta receptors from invertebrates, such as starfish and worms, and dissecting their evolutionary history, we identify mutations that occurred during evolution to make the vertebrate homoloues inactive. Furthermore, we find that GABA, the classical inhibitory neurotransmitter, activates these excitatory receptors in invertebrates.

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Why is it important?

Delta-type ionotropic glutamate receptors (iGluRs) have been relatively refractive to experimental dissection because of the inactivity of mammalian delta iGluRs. By characterizing robust GABA-induced activity of various invertebrate delta iGluRs, we (1) enable future studies dissecting the structure, function, and pharmacology of delta iGluRs and (2) suggest that the classical inhibitory neurotransmitter, GABA, may be mediating excitatory signaling in numerous animals.


It's great to see that dissecting evolution can uncover biophysical mechanisms, and in turn, biophysical experiments help uncover suprising twists in protein evolution.

Timothy Lynagh
University of Bergen

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This page is a summary of: Loss of activation by GABA in vertebrate delta ionotropic glutamate receptors, Proceedings of the National Academy of Sciences, January 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2313853121.
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