| Autor: |
Seong, E., Wainer, B. H., Hughes, E. D., Saunders, T. L., Burmeister, M., Faundez, V. |
| Zdroj: |
Molecular Biology of the Cell; January 2005, Vol. 16 Issue: 1 p128-140, 13p |
| Abstrakt: |
Neurons express adaptor (AP)-3 complexes assembled with either ubiquitous (β3A) or neuronal-specific (β3B) β3 isoforms. However, it is unknown whether these complexes indeed perform distinct functions in neuronal tissue. Here, we explore this hypothesis by using genetically engineered mouse models lacking either β3A- or β3B-containing AP-3 complexes. Somatic and neurological phenotypes were specifically associated with the ubiquitous and neuronal adaptor deficiencies, respectively. At the cellular level, AP-3 isoforms were localized to distinct neuronal domains. β3B-containing AP-3 complexes were preferentially targeted to neuronal processes. Consistently, β3B deficiency compromised synaptic zinc stores assessed by Timm's staining and the synaptic vesicle targeting of membrane proteins involved in zinc uptake (ZnT3 and ClC-3). Surprisingly, despite the lack of neurological symptoms, β3A-deficient mouse brain possessed significantly increased synaptic zinc stores and synaptic vesicle content of ZnT3 and ClC-3. These observations indicate that the functions of β3A- and β3B-containing complexes are distinct and divergent. Our results suggest that concerted nonredundant functions of neuronal and ubiquitous AP-3 provide a mechanism to control the levels of selected membrane proteins in synaptic vesicles. |
| Databáze: |
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