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The Journal of Neuroscience, April 7, 2004, 24(14):3711-3720; doi:10.1523/JNEUROSCI.5225-03.2004
 Previous Article
Cellular/Molecular
Molecular Determinants of Synapsin Targeting to Presynaptic Terminals
Daniel Gitler,1
Yimei Xu,1
Hung-Teh Kao,2,3
Dayu Lin,1
Sangmi Lim,1
Jian Feng,2,4
Paul Greengard,2 and
George J. Augustine1
1Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, 2Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York 10021, 3Center for Dementia Research, Nathan Kline Institute, and Department of Psychiatry, New York University School of Medicine, Orangeburg, New York 10962, and 4Department of Physiology and Biophysics, State University of New York, Buffalo, New York 14214
Although synapsins are abundant synaptic vesicle proteins that are widely used as markers of presynaptic terminals, the mechanisms that target synapsins to presynaptic terminals have not been elucidated. We have addressed this question by imaging the targeting of green fluorescent protein-tagged synapsins in cultured hippocampal neurons. Whereas all synapsin isoforms targeted robustly to presynaptic terminals in wild-type neurons, synapsin Ib scarcely targeted in neurons in which all synapsins were knocked-out. Coexpression of other synapsin isoforms significantly strengthened the targeting of synapsin Ib in knock-out neurons, indicating that heterodimerization is required for synapsin Ib to target. Truncation mutagenesis revealed that synapsin Ia targets via distributed binding sites that include domains B, C, and E. Although domain A was not necessary for targeting, its presence enhanced targeting. Domain D inhibited targeting, but this inhibition was overcome by domain E. Thus, multiple intermolecular and intramolecular interactions are required for synapsins to target to presynaptic terminals.
Key words: localization; presynaptic; synapsin; synaptic vesicles; synaptic transmission; synaptic vesicle trafficking; presynaptic localization; vesicle pools
Received Nov 25, 2003;
revised February 25, 2004;
accepted February 27, 2004.
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