Institute of Medical Physics and Biophysics, University of Münster, Münster, Germany.
EMBO J. 2010 Apr 21;29(8):1318-30. doi: 10.1038/emboj.2010.15. Epub 2010 Mar 4.
Synaptic vesicle recycling involves AP-2/clathrin-mediated endocytosis, but it is not known whether the endosomal pathway is also required. Mice deficient in the tissue-specific AP-1-sigma1B complex have impaired synaptic vesicle recycling in hippocampal synapses. The ubiquitously expressed AP-1-sigma1A complex mediates protein sorting between the trans-Golgi network and early endosomes. Vertebrates express three sigma1 subunit isoforms: A, B and C. The expressions of sigma1A and sigma1B are highest in the brain. Synaptic vesicle reformation in cultured neurons from sigma1B-deficient mice is reduced upon stimulation, and large endosomal intermediates accumulate. The sigma1B-deficient mice have reduced motor coordination and severely impaired long-term spatial memory. These data reveal a molecular mechanism for a severe human X-chromosome-linked mental retardation.
突触囊泡循环涉及 AP-2/网格蛋白介导的内吞作用，但尚不清楚内体途径是否也是必需的。组织特异性 AP-1-σ1B 复合物缺陷的小鼠在海马突触中突触囊泡循环受损。广泛表达的 AP-1-σ1A 复合物介导跨高尔基网络和早期内体之间的蛋白质分拣。脊椎动物表达三种 σ1 亚基同工型：A、B 和 C。σ1A 和 σ1B 的表达在大脑中最高。刺激后，来自 σ1B 缺陷型小鼠的培养神经元中的突触囊泡再形成减少，并且大的内体中间产物积累。σ1B 缺陷型小鼠运动协调性降低，长期空间记忆严重受损。这些数据揭示了一种严重的人类 X 连锁智力低下的分子机制。
