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-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.
Glyvuk
Nataliya
N
Institute of Medical Physics and Biophysics, University of Münster, Münster, Germany.
Tsytsyura
Yaroslav
Y
Geumann
Constanze
C
D'Hooge
Rudi
R
Hüve
Jana
J
Kratzke
Manuel
M
Baltes
Jennifer
J
Boening
Daniel
D
Böning
Daniel
D
Klingauf
Jürgen
J
Schu
Peter
P
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*
D033961:Adaptor Protein Complex 1; D002966:Clathrin; D020033:Protein Isoforms