Abstract
Heterotetrameric adaptor complexes vesiculate donor membranes. One of the adaptor protein complexes, AP-3, is present in two forms; one form is expressed in all tissues of the body, whereas the other is restricted to brain. Mice lacking both the ubiquitous and neuronal forms of AP-3 exhibit neurological disorders that are not observed in mice that are mutant only in the ubiquitous form. To begin to understand the role of neuronal AP-3 in neurological disease, we investigated its function in in vitro assays as well as its localization in neural tissue. In the presence of GTPgammaS both ubiquitous and neuronal forms of AP-3 can bind to purified synaptic vesicles. However, only the neuronal form of AP-3 can produce synaptic vesicles from endosomes in vitro. We also identified that the expression of neuronal AP-3 is limited to varicosities of neuronal-like processes and is expressed in most axons of the brain. Although the AP-2/clathrin pathway is the major route of vesicle production and the relatively minor neuronal AP-3 pathway is not necessary for viability, the absence of the latter could lead to the neurological abnormalities seen in mice lacking the expression of AP-3 in brain. In this study we have identified the first brain-specific function for a neuronal adaptor complex.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Vesicular Transport
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Adenosine Triphosphate / metabolism
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Animals
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Antibodies / pharmacology
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Axons / metabolism
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Brain / metabolism
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Brain Chemistry
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Carrier Proteins / analysis
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / metabolism*
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Cell Line
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Cell-Free System / chemistry
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Cell-Free System / metabolism
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Cytosol / chemistry
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Cytosol / metabolism
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Endosomes / metabolism*
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Female
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Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
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Humans
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Membrane Proteins / analysis
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mice, Mutant Strains
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Monomeric Clathrin Assembly Proteins*
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Neurons / cytology
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Neurons / metabolism*
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Organ Specificity
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PC12 Cells
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Protein Isoforms / analysis
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Protein Isoforms / antagonists & inhibitors
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Protein Isoforms / metabolism
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R-SNARE Proteins
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Rats
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Rats, Sprague-Dawley
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Synaptic Vesicles / chemistry
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Synaptic Vesicles / drug effects
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Synaptic Vesicles / metabolism*
Substances
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Adaptor Proteins, Vesicular Transport
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Antibodies
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Carrier Proteins
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Membrane Proteins
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Monomeric Clathrin Assembly Proteins
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Protein Isoforms
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R-SNARE Proteins
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clathrin assembly protein AP180
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Guanosine 5'-O-(3-Thiotriphosphate)
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Adenosine Triphosphate