title: AP-1/sigma1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory.
abstract: 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.
authors.affiliation: Institute of Medical Physics and Biophysics, University of Münster, Münster, Germany.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Glyvuk
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Tsytsyura
authors.forename: Constanze
authors.initials: C
authors.lastname: Geumann
authors.forename: Rudi
authors.initials: R
authors.lastname: D'Hooge
authors.forename: Jana
authors.initials: J
authors.lastname: Hüve
authors.forename: Manuel
authors.initials: M
authors.lastname: Kratzke
authors.forename: Jennifer
authors.initials: J
authors.lastname: Baltes
authors.forename: Daniel
authors.initials: D
authors.lastname: Boening
authors.forename: Daniel
authors.initials: D
authors.lastname: Böning
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klingauf
authors.forename: Peter
authors.initials: P
authors.lastname: Schu
mesh_terms: D033961:Adaptor Protein Complex 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007858:Learning; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D009474:Neurons / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D033961:Adaptor Protein Complex 1; D002966:Clathrin; D020033:Protein Isoforms