Synaptic vesicle recycling: Molecular functions of the AP-1 complex subunit σ1B-adaptin

The adaptor-protein complex AP-1, which consists of the four adaptins γ1, β1, µ1 and σ1, mediates protein sorting via transport vesicles between the trans-Golgi network and endosomes. In vertebrates three isoforms of the σ1 subunit are expressed: A, B and C. σ1A is ubiquitously expressed, while σ1B shows highest expression in the brain. σ1B-‘knock-out’ mice develop normally, but they have impaired long-term spatial memory and reduced motor coordination. Hippocampal synapses have reduced synaptic vesicle numbers and after stimulation of synaptic vesicle recycling, synaptic vesicle reformation is reduced and large endosomal intermediates accumulate. In synaptic vesicle recycling AP-2/clathrin-mediated endocytosis is involved, but it is not known, whether the endosomal pathway is also required. Impaired synaptic vesicle recycling in AP-1/σ1B-deficient neurons indicates that AP-1 plays a role in SV recycling through endosomal structures. In σ1B-‘knock-out’ brain extracts a reduction in the γ1 protein level is not detectable, however less of γ1 is found in the synaptosomal fraction. Adaptins are only stable, if incorporated into an AP-complex and therefore the reduced γ1 levels strongly indicate AP-1/σ1B-complex localization to synapses. Synaptosomal membranes were subfractionated to analyze alterations in their protein composition due to σ1B-deficiency.