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

点击翻译按钮获取中文摘要

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.