Huntingtin-associated protein 1 regulates inhibitory synaptic transmission by modulating γ-aminobutyric acid type A receptor membrane trafficking
Huntingtin-associated protein 1 regulates inhibitory synaptic transmission by modulating γ-aminobutyric acid type A receptor membrane trafficking
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DOI：
10.1073/pnas.0401860101
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发表时间：
2004-08-24
影响因子：
11.1
通讯作者：
Moss, SJ
中科院分区：
文献类型：
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作者：
Kittler, JT;Thomas, P;Moss, SJ
γ-氨基丁酸A型受体（GABA（A）Rs）是脑中快速突触抑制的主要部位。突触抑制功效的一个重要决定因素是GABA（A）R细胞表面稳定性的调节。在这里，我们研究了GABA（A）R内吞分选的调节，细胞表面受体数量的关键调节器。在神经元中，GABA（A）Rs的快速组成性内吞是明显的。然后，内化的受体要么迅速再循环回到细胞表面，要么在较慢的时间尺度上，靶向溶酶体降解。这种分选决定受GABA（A）Rs与亨廷顿相关蛋白1（HAP 1）的直接相互作用的调节。HAP 1通过抑制受体降解和促进受体再循环来调节突触GABA（A）R数量。总之，这些观察结果已经确定了HAP 1在调节GABAAR分选中的作用，表明这种蛋白质在抑制性突触的构建和维持中具有重要作用。
gamma-Aminobutyric acid type A receptors (GABA(A)Rs) are the major sites of fast synaptic inhibition in the brain. An essential determinant for the efficacy of synaptic inhibition is the regulation of GABA(A)R cell surface stability. Here, we have examined the regulation of GABA(A)R endocytic sorting, a critical regulator of cell surface receptor number. In neurons, rapid constitutive endocytosis of GABA(A)Rs was evident. Internalized receptors were then either rapidly recycled back to the cell surface, or on a slower time scale, targeted for lysosomal degradation. This sorting decision was regulated by a direct interaction of GABA(A)Rs with Huntingtin-associated protein 1 (HAP1). HAP1 modulated synaptic GABA(A)R number by inhibiting receptor degradation and facilitating receptor recycling. Together these observations have identified a role for HAP1 in regulating GABAAR sorting, suggesting an important role for this protein in the construction and maintenance of inhibitory synapses.