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The protein MAP-1B links GABAC receptors to the cytoskeleton at retinal synapses

Nature volume 397, pages 66–69 (1999)Cite this article

Abstract

The ionotropic type-A and type-C receptors for the neurotransmitter γ-aminobutyric acid (GABAA and GABAC receptors) are the principal sites of fast synaptic inhibition in the central nervous system1,2,3, but it is not known how these receptors are localized at GABA-dependent synapses. GABAC receptors, which are composed of ρ-subunits3,4,5,6, are expressed almost exclusively inthe retina of adult vertebrates, where they are enriched on bipolar cell axon terminals7,8,9. Here we show that the microtubule-associated protein 1B (MAP-1B) specifically interacts with the GABAC ρ1 subunit but not with GABAA receptor subunits. Furthermore, GABAC receptors and MAP-1B co-localize at postsynaptic sites on bipolar cell axon terminals. Co-expression of MAP-1B and the ρ1 subunit in COS cells results in a dramatic redistribution of the ρ1 subunit. Our observations suggest a novel mechanism for localizing ionotropic GABA receptors to synaptic sites. This mechanism, which is specific for GABAC but not GABAA receptors, may allow these receptor subtypes, which have distinct physiological and pharmacological properties, to be differentially localized at inhibitory synapses.

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Figure 1: Specific interaction of the ρ1 intracellular domain with an N-terminal domain of MAP-1B.
Figure 2: Interaction of MAP-1B with the GABAC receptor ρ1 subunit in retinal extracts.
Figure 3: Co-localization of ρ-subunits and MAP-1B immunoreactivity in the retina.
Figure 4: Co-expression of MAP-1B and the ρ1 subunit in COS cells induces redistribution of the ρ1 subunit.

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Acknowledgements

We thank C.-H. Sung for the retinal cDNA library, D. Attwell for help with retinal cultures, and W. Wisden and T. Smart for their comments on the manuscript. This work was supported by the MRC, the Wellcome Trust and the Royal Society.

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Authors and Affiliations

  1. MRC Laboratory for Molecular Cell Biology and Department of Pharmacology, University College, Gower Street, WC1E 6BT, London, UK

    Jonathan G. Hanley, Fiona Bedford & Stephen J. Moss

  2. Neuroanatomische Abteilung, Max-Plank-Institut fur Hirnforschung, Deutschordenstrasse 46, 60528, Frankfurt, Germany

    Peter Koulen

  3. Division of Biomedical Sciences, Developmental Biology Research Centre, Kings College London, 2629 Dury Lane, WC2B 5RL, London, UK

    Phillip R. Gordon-Weeks

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Correspondence to Stephen J. Moss.

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Hanley, J., Koulen, P., Bedford, F. et al. The protein MAP-1B links GABAC receptors to the cytoskeleton at retinal synapses. Nature 397, 66–69 (1999). https://doi.org/10.1038/16258

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