The protein MAP-1B links GABA(c) receptors to the cytoskeleton at retinal synapses

The ionotropic type-A and type-C receptors for the neurotransmitter gamma-a minobutyric acid (GABA(A) and GABA(C) receptors) are the principal sites of fast synaptic inhibition in the central nervous system(1-3), but it is not known how these receptors are localized at GABA-dependent synapses. GABA(C ) receptors, which are composed of rho-subunits(3-6), are expressed almost exclusively in the retina of adult vertebrates, where they are enriched on bipolar cell axon terminals(7-9). Here we show that the microtubule-associa ted protein 1B (MAP-1B) specifically interacts with the GABA(C) pi subunit but not with GABA(A) receptor subunits. Furthermore, GABA(C) receptors and MAP-1B co-localize at postsynaptic sites on bipolar cell axon terminals. Co -expression of MAP-1B and the pi subunit in COS cells results in a dramatic redistribution of the rho 1 subunit. Our observations suggest a novel mech anism for localizing ionotropic GABA receptors to synaptic sites. This mech anism, which is specific for GABA(C) but not GABA(A) receptors, may allow t hese receptor subtypes, which have distinct physiological and pharmacologic al properties, to be differentially localized at inhibitory synapses.