Structural difference between heteromeric somatic and homomeric axonal glycine receptors in the hypothalamo-neurohypophysial system

Deleuze, Charlotte; Runquist, M.; Orcel, Hélène; Rabié, A.; Dayanithi, Govindan; Alonso, Gérard; Hussy, Nicolas

doi:10.1016/j.neuroscience.2005.05.024

Cited by 23 publications

(16 citation statements)

References 42 publications

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“…Second, the homomer to heteromer ratio when α and β-subunits are co-expressed suggests that there is not a strong bias toward association of α with β during channel assembly in oocytes. An interesting question is whether factors besides the relative affinity of α-subunits for β-subunits account for the proportion of extra-synaptic α-homomers in vivo (Turecek and Trussell, 2002; Deleuze et al, 2005). Third, α-subunit homomers form functional glycine receptors and therefore α-α subunit interfaces can bind glycine and gate GlyRs.…”

Section: Discussionmentioning

confidence: 99%

“…Third, α-subunit homomers form functional glycine receptors and therefore α-α subunit interfaces can bind glycine and gate GlyRs. Homomeric GlyRs are thought to be presynaptic while heteromeric GlyRs are synaptic (Kirsch et al, 1993; Turecek and Trussell, 2001; Turecek and Trussell, 2002; Deleuze et al, 2005). It could be useful to develop drugs that specifically target presynaptic over postsynaptic channels or vice versa.…”

Section: Discussionmentioning

confidence: 99%

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Stoichiometry of the Human Glycine Receptor Revealed by Direct Subunit Counting

et al. 2012

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The subunit stoichiometry of heteromeric glycine-gated channels (GlyRs) determines fundamental properties of these key inhibitory neurotransmitter receptors; however the ratio of α1 to β-subunits per receptor remains controversial. We used single molecule imaging and stepwise photobleaching in Xenopus oocytes to directly determine the subunit stoichiometry of a glycine receptor to be 3α1:2β. This approach allowed us to determine the receptor stoichiometry in mixed populations consisting of both heteromeric and homomeric channels, additionally revealing the quantitative proportions for the two populations.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Stoichiometry of the Human Glycine Receptor Revealed by Direct Subunit Counting

et al. 2012

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“…This is consistent with our notion of the presence of two different subtypes of glycine receptors in the OPL and IPL, located on the dendrites and the axons of the bipolar cells, respectively. Recently, two different subtypes of glycine receptors were localized in the somatodendritic and the axonal membrane of the supraoptic nucleus neurons as well (Deleuze et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Immunocytochemical study of glycine receptors in the retina of the frog Xenopus laevis

Vitanova

2006

Anat Embryol

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The expression of glycine receptors in the retina of clawed frog, Xenopus laevis was studied immunocytochemically. Glycine receptors (GlyRs), as revealed by means of several different antibodies, were mainly distributed in the inner (IPL) and the outer plexiform layers. Their composition was determined to include alpha2 and alpha3 subunits. Typical punctate appearance and specific lamination in the IPL were seen with each of the antibodies directed against the different GlyRs' subunits. A notion for diversity of the glycine receptors was put forward, according to which the alpha2 and alpha3 subunits are located in different subtypes of glycine synapses.

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“…Low concentrations of PTX have been shown to preferentially inhibit homomeric α GlyRs without significantly altering heteromeric αβ GlyRs expressed in HEK-293 cells 21, 22 . Similarly, PTX at low doses is also found to selectively affect presynaptic GlyRs, which are likely homomers, in the spinal cord and brainstem 7, 9, 23 . We first examined the sensitivity of homomeric and heteromeric α1R271Q mutant GlyRs to PTX-induced inhibition when expressed in HEK-293 cells.…”

Section: Resultsmentioning

confidence: 92%

Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease

Xiong

Chen

et al. 2014

Nat Neurosci

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While postsynaptic GlyRs as α/β heteromers attract the most research attention, little is known about the role of presynaptic GlyRs, likely α homomers, in diseases. Here, we demonstrate that DH-CBD, a nonpsychoactive cannabinoid, can rescue GlyR functional deficiency and exaggerated acoustic and tactile startle responses in mice bearing the point-mutations in the α1 GlyRs responsible for a hereditary startle/hyperekplexia disease. The GlyRs expressed as α1 homomers either in HEK-293 cells or at presynaptic terminals of the calyceal synapses in auditory brainstem are most vulnerable to hyperekplexia mutation-induced impairment. Homomeric mutants are more sensitive than heteromers to DH-CBD, suggesting presynaptic GlyRs as a primary target. Consistent with this, DH-CBD selectively rescues impaired presynaptic GlyR activity and diminished glycine release in the brainstem and spinal cord of hyperekplexic mutant mice. Thus, presynaptic α GlyRs emerge as a potential therapeutic target for dominant hyperekplexia disease and other diseases with GlyR deficiency.

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Structural difference between heteromeric somatic and homomeric axonal glycine receptors in the hypothalamo-neurohypophysial system

Cited by 23 publications

References 42 publications

Stoichiometry of the Human Glycine Receptor Revealed by Direct Subunit Counting

Stoichiometry of the Human Glycine Receptor Revealed by Direct Subunit Counting

Immunocytochemical study of glycine receptors in the retina of the frog Xenopus laevis

Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease

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