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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 GTPgamma 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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