Molecular Determinants of Synapsin Targeting to Presynaptic Terminals

Daniel Gitler, Yimei Xu, Hung Teh Kao, Dayu Lin, Sangmi Lim, Jian Feng, Paul Greengard, George J. Augustine

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

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 pre-synaptic 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.

Original languageEnglish
Pages (from-to)3711-3720
Number of pages10
JournalJournal of Neuroscience
Volume24
Issue number14
DOIs
StatePublished - 7 Apr 2004
Externally publishedYes

Keywords

  • Localization
  • Presynaptic
  • Presynaptic localization
  • Synapsin
  • Synaptic transmission
  • Synaptic vesicle trafficking
  • Synaptic vesicles
  • Vesicle pools

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