Neuronal and non-neuronal functions of the AP-3 sorting machinery.

ABSTRACT

Vesicles selectively exchange lipids, membrane proteins and luminal contents between organelles along the exocytic and endocytic routes. The repertoire of membrane proteins present in these vesicles is crucial for their targeting and function. Vesicle composition is determined at the time of their biogenesis by cytosolic coats. The heterotetrameric protein adaptor protein complex 3 (AP-3), a coat component, participates in the generation of a diverse group of secretory organelles and lysosome-related organelles. Recent work has shed light on the mechanisms that regulate AP-3 and the trafficking pathways controlled by this adaptor. Phenotypic analysis of organisms carrying genetic deficiencies in the AP-3 pathway highlight its role regulating the targeting of lysosomal, melanosomal and synaptic vesicle-specific membrane proteins. Synaptic vesicles from AP-3-deficient mice possess altered levels of neurotransmitter and ion transporters, molecules that ultimately define the type and amount of neurotransmitter stored in these vesicles. These findings reveal a complex picture of how AP-3 functions in multiple tissues, including neuronal tissue, and expose potential links between endocytic sorting mechanisms and the pathogenesis of psychiatric disorders such as schizophrenia.