The protein MAP-1B links GABAc receptors to the cytoskeleton at retinal synapses
The protein MAP-1B links GABAc receptors to the cytoskeleton at retinal synapses
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作者：
Hanley, JG;Koulen, P;Moss, SJ
神经递质γ -氨基丁酸(GABA（A)和GABA(C)受体）的嗜离子性A型和C型受体是中枢神经系统中快速突触抑制的主要位点（1-3），但目前尚不清楚这些受体如何定位于GABA依赖性突触。GABA(C)受体由rho亚基组成（3-6），几乎只在成年脊椎动物的视网膜中表达，在双极细胞轴突末端富集（7-9）。本研究表明，微管相关蛋白1B （MAP-1B）特异性地与GABA(C) pi亚基相互作用，但不与GABA(A)受体亚基相互作用。此外，GABA(C)受体和MAP-1B共定位于双极细胞轴突末端的突触后位点。MAP-1B和pi亚基在COS细胞中的共表达导致rho 1亚基的重新分布。我们的观察结果提示了一种新的将嗜离子氨基丁酸受体定位到突触位点的机制。这种机制是GABA(C)特异性的，而不是GABA(A)受体，可能允许这些具有不同生理和药理学特性的受体亚型在抑制性突触上有不同的定位。
The ionotropic type-A and type-C receptors for the neurotransmitter gamma-aminobutyric 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-associated 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 mechanism for localizing ionotropic GABA receptors to synaptic sites. This mechanism, which is specific for GABA(C) but not GABA(A) receptors, may allow these receptor subtypes, which have distinct physiological and pharmacological properties, to be differentially localized at inhibitory synapses.