Long distance effect on ligand-gated ion channels extracellular domain may affect interactions with the intracellular machinery.
Communicative & Integrative Biology. 2014-01-30; 7(1): e27984
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1. Commun Integr Biol. 2014 Feb 6;7:e27984. doi: 10.4161/cib.27984. eCollection
Long distance effect on ligand-gated ion channels extracellular domain may affect
interactions with the intracellular machinery.
Garret M(1), Boué-Grabot E(2), Taly A(3).
(1)Univ. Bordeaux; INCIA; UMR 5287; Bordeaux, France ; CNRS; INCIA; UMR 5287;
(2)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France ; CNRS; Institut des Maladies Neurodégénératives; UMR 5293;
(3)Laboratoire de Biochimie Théorique (CNRS-Université Paris Diderot); Paris,
Modulation of receptor trafficking is critical for controlling neurotransmission.
A γ2(R43Q) point mutation on GABAA receptor subunit is linked to epilepsy in
human. We recently analyzed the effect of this amino-acid substitution on GABAA
receptor trafficking and showed that this mutation as well as agonist
application, both affecting GABAA receptor extracellular domain, have an effect
on receptor endocytosis. By comparing homology models based on ligand gated ion
channels in their active and resting states, we reveal that the γ2R43 domain is
located in a loop that is affected by motion resulting from receptor activation.
Taken together, these results suggest that endocytosis of GABAA receptors is
linked to agonist induced conformational changes. We propose that ligand or
modulator binding is followed by a whole chain of interconnections, including the
intracellular domain, that may influence ligand-gated channel trafficking.