AP-1/sigma 1B-Dependent SV Protein Recycling Is Regulated in Early Endosomes and Is Coupled to AP-2 Endocytosis
2015 | journal article. A publication with affiliation to the University of Göttingen.
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- Authors
- Kratzke, Manuel; Candiello, Ermes ; Schmidt, Bernhard; Jahn, Olaf ; Schu, Peter
- Abstract
- Adaptor protein (AP)-1/sigma 1B(-/-) mice have reduced synaptic-vesicle (SV) recycling and increased endosomes. Mutant mice have impaired spatial memory, and sigma 1B-deficient humans have a severe mental retardation. In order to define these sigma 1B(-/-) 'bulk' endosomes and to determine their functions in SV recycling, we developed a protocol to separate them from the majority of the neuronal endosomes. The sigma 1B(-/-) 'bulk' endosomes proved to be classic early endosomes with an increase in the phospholipid phosphatidylinositol 3-phosphate (PI-3-P), which recruits proteins mediating protein sorting out of early endosomes into different routes. sigma 1B deficiency induced alterations in the endosomal proteome reveals two major functions: SV protein storage and sorting into endolysosomes. Alternative endosomal recycling pathways are not up-regulated, but certain SV proteins are misrouted. Tetraspanins are enriched in sigma 1B(-/-) synaptosomes, but not in their endosomes or in their clathrin-coated-vesicles (CCVs), indicating AP-1/sigma 1B-dependent sorting. Synapses contain also more AP-2 CCV, although it is expected that they contain less due to reduced SV recycling. Coat composition of these AP-2 CCVs is altered, and thus, they represent a subpopulation of AP-2 CCVs. Association of calmodulin-dependent protein kinase (CaMK)-II alpha, -delta and casein kinase (CK)-II alpha with the endosome/SV pool is altered, as well as 14-3-3 eta, indicating changes in specific signalling pathways regulating synaptic plasticity. The accumulation of early endosomes and endocytotic AP-2 CCV indicates the regulation of SV recycling via early endosomes by the interdependent regulation of AP-2-mediated endocytosis and AP-1/sigma 1B-mediated SV reformation.
- Issue Date
- 2015
- Status
- published
- Publisher
- Humana Press Inc
- Journal
- Molecular Neurobiology
- ISSN
- 1559-1182; 0893-7648
- Sponsor
- DFG [Schu 802/3-1, 802/3-2]