Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Neuron. 2012 Sep 6;75(5):810-23. doi: 10.1016/j.neuron.2012.07.007.
Plasma membranes of the somatodendritic and axonal domains of neurons are known to have different protein compositions, but the molecular mechanisms that determine this polarized protein distribution remain poorly understood. Herein we show that somatodendritic sorting of various transmembrane receptors in rat hippocampal neurons is mediated by recognition of signals within the cytosolic domains of the proteins by the μ1A subunit of the adaptor protein-1 (AP-1) complex. This complex, in conjunction with clathrin, functions in the neuronal soma to exclude somatodendritic proteins from axonal transport carriers. Perturbation of this process affects dendritic spine morphology and decreases the number of synapses. These findings highlight the primary recognition event that underlies somatodendritic sorting and contribute to the evolving view of AP-1 as a global regulator of cell polarity.
神经元的树突和轴突区域的质膜具有不同的蛋白质组成，但决定这种极化蛋白质分布的分子机制仍知之甚少。本文中，我们发现大鼠海马神经元中各种跨膜受体的树突-轴突分拣是由衔接蛋白 1（AP-1）复合物的 μ1A 亚基识别蛋白胞质域内的信号介导的。该复合物与网格蛋白一起在神经元胞体中发挥作用，将树突-轴突蛋白排除在轴突运输载体之外。该过程的破坏会影响树突棘形态并减少突触数量。这些发现强调了树突-轴突分拣的主要识别事件，并为 AP-1 作为细胞极性的全局调节剂的不断发展的观点做出了贡献。
