AP-1/σ1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory
Glyvuk, Nataliya × Tsytsyura, Yaroslav Geumann, Constanze D'Hooge, Rudi Hüve, Jana Kratzke, Manuel Baltes, Jennifer Böning, Daniël Klingauf, Jürgen Schu, Peter #
Nature Publishing Group
EMBO Journal vol:29 issue:8 pages:1318-1330
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–σ1B complex have impaired synaptic vesicle recycling in hippocampal synapses. The ubiquitously expressed AP-1–σ1A complex mediates protein sorting between the trans-Golgi network and early endosomes. Vertebrates express three σ1 subunit isoforms: A, B and C. The expressions of σ1A and σ1B are highest in the brain. Synaptic vesicle reformation in cultured neurons from σ1B-deficient mice is reduced upon stimulation, and large endosomal intermediates accumulate. The σ1B-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.