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  • The EMBO Journal (2006) 25, 4381 - 4389
  • doi:10.1038/sj.emboj.7601309

Published online: 31 August 2006

Synaptic GABAA receptors are directly recruited from their extrasynaptic counterparts

Yury Bogdanov1,2, Guido Michels1,2,3, Cecilia Armstrong-Gold1, Philip G Haydon1, Jon Lindstrom1, Menelas Pangalos4 and Stephen J Moss1,2

  1. Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA
  2. Department of Pharmacology, University College, London, UK
  3. Department of Internal Medicine III, University of Cologne, Cologne, Germany
  4. Wyeth Research, Neuroscience Discovery, Princeton, NJ, USA

Correspondence to:

Stephen J Moss, Department of Neuroscience, University of Pennsylvania, 145 Johnson Pavilion, Hamilton Walk, Philadelphia, PA 19104, USA. Tel.: +1 215 898 1998; Fax: +1 215 898 1347; E-mail: sjmoss@mail.med.upenn.edu

Received 27 April 2006; Accepted 3 August 2006

GABAA receptors mediate the majority of fast synaptic inhibition in the brain. The accumulation of these ligand-gated ion channels at synaptic sites is a prerequisite for neuronal inhibition, but the molecular mechanisms underlying this phenomenon remain obscure. To further understand these processes, we have examined the cellular origins of synaptic GABAA receptors. To do so, we have created fluorescent GABAA receptors that are capable of binding alpha-bungarotoxin (Bgt), facilitating the visualization of receptor endocytosis, exocytosis and delivery to synaptic sites. Imaging with Bgt in hippocampal neurons revealed that GABAA receptor endocytosis occurred exclusively at extrasynaptic sites, consistent with the preferential colocalization of extrasynaptic receptors with the AP2 adaptin. Receptor insertion into the plasma membrane was also predominantly extrasynaptic, and pulse-chase analysis revealed that these newly inserted receptors were then able to access directly synaptic sites. Therefore, our results demonstrate that synaptic GABAA receptors are directly recruited from their extrasynaptic counterparts. Moreover, they illustrate a dynamic mechanism for neurons to modulate GABAA receptor number at inhibitory synapses by controlling the stability of extrasynaptic receptors.

  • Keywords:

    • bungarotoxin binding site,
    • endocytosis,
    • exocytosis,
    • GABAA receptor,
    • inhibitory synaptic sites