AP-1/sigma1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory.

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-sigma 1B complex have impaired synaptic vesicle recycling in hippocampal synapses. The ubiquitously expressed AP-1-sigma 1A complex mediates protein sorting between the trans-Golgi network and early endosomes. Vertebrates express three sigma 1 subunit isoforms: A, B and C. The expressions of sigma 1A and sigma 1B are highest in the brain. Synaptic vesicle reformation in cultured neurons from sigma 1B-deficient mice is reduced upon stimulation, and large endosomal intermediates accumulate. The sigma 1B-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. The EMBO Journal (2010) 29, 1318-1330. doi: 10.1038/emboj.2010.15; Published online 4 March 2010