Mechanisms for regulation of intracellular protein sorting mediated by the adaptor protein (AP) complex family

上皮细胞的质膜（PM）在物理上被紧密连接分为顶端和底外侧结构域，不同的膜蛋白亚群在这两个结构域上表达。我们克隆了一个新的μ同系物μ lb，它只在上皮细胞中表达。AP-1B含有μ1B，介导新合成蛋白对基底侧PM的选择性分选。脊髓灰质炎病毒受体（PVR）有α和δ两种亚型。我们发现PVRα与μlB相互作用并在基底侧表达，而PVRδ不被μ1B识别，在两个PM结构域上随机表达。我们还发现，缺乏μ1B的上皮细胞分裂是随机的，导致上皮细胞呈现多层形态，而不是单层的特征。为了研究μlB在生物体中的作用，我们建立了制备μ1B敲除小鼠的ES细胞系。我们还建立了缺乏μ3B的小鼠，μ3B是神经元特异性AP -3B复合物的一个亚基。μ3B KO小鼠出现癫痫发作。在这些小鼠中，kcl刺激海马切片中GABA（一种抑制性神经递质）的释放减少到野生型小鼠的一半，表明抑制性突触传递的中断导致了癫痫发作。

Plasma membrane (PM) of epithelial cells is physically divided by the tight junction into apical and basolateral domains, and distinct subsets of membrane proteins are expressed on the two domains. We cloned a new μ homologue, μlB, which is expressed exclusively in epithelial cells. AP-1B, containing μ1B, mediates selective sorting of newly synthesized proteins to the basolateral PM. There are two isoforms for poliovirus receptor (PVR), α and δ. We have found that PVRα interacts with μlB and expressed basolaterally, whereas PVRδ is not recognized by μ1B and randomly expressed on both PM domains. We also found that μ1B- deficient epithelial cells divide randomly, causing multi-layer morphology instead of monolayer characteristic to epithelial cells. In order to investigate the roles of μlB in organisms, we established ES cell lines for making μ1B knockout mice.We also established mice lacking μ3B, a subunit of the neuron-specific AP -3B complex. μ3B KO mice suffer from epileptic seizure. In these mice, KCl-stimulated release of GABA, an inhibitory neurotransmitter, from hippocampal slices decreased to one-half of that of wild-type mice, suggesting that break down in inhibitory synaptic transmission cause the seizure.