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The Journal of Neuroscience, October 15, 2001, 21(20):8034-8042
The Neuronal Form of Adaptor Protein-3 Is Required for Synaptic
Vesicle Formation from Endosomes
Jessica
Blumstein1,
Victor
Faundez2,
Fubito
Nakatsu3, 4,
Takashi
Saito4,
Hiroshi
Ohno3, and
Regis B.
Kelly1
1 Department of Biochemistry and Biophysics, University
of California, San Francisco, California 94143-0448, 2 Department of Cell Biology, Emory University, Atlanta,
Georgia 30322, 3 Division of Molecular Membrane Biology,
Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa
920-0934, Japan, and 4 Department of Molecular Genetics,
Chiba University Graduate School of Medicine, Chuoka, Chiba 260-8670, Japan
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 GTP S 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.
Key words:
adaptor protein; synaptic vesicle; AP-3; endosome; brain; neuronal isoforms
Copyright © 2001 Society for Neuroscience 0270-6474/01/21208034-09$05.00/0
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