期刊
JOURNAL OF NEUROSCIENCE
卷 24, 期 14, 页码 3711-3720出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5225-03.2004
关键词
localization; presynaptic; synapsin; synaptic vesicles; synaptic transmission; synaptic vesicle trafficking; presynaptic localization; vesicle pools
资金
- NIMH NIH HHS [R37 MH039327, R01 MH039327, MH 39327, MH 67044, R01 MH067044] Funding Source: Medline
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.
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