Tweek, an Evolutionarily Conserved Protein, Is Required for Synaptic Vesicle Recycling

Patrik Verstreken, Tomoko Ohyama, Claire Haueter, Ron L.P. Habets, Yong Q. Lin, Laura E. Swan, Cindy V. Ly, Koen J.T. Venken, Pietro De Camilli, Hugo J. Bellen

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Synaptic vesicle endocytosis is critical for maintaining synaptic communication during intense stimulation. Here we describe Tweek, a conserved protein that is required for synaptic vesicle recycling. tweek mutants show reduced FM1-43 uptake, cannot maintain release during intense stimulation, and harbor larger than normal synaptic vesicles, implicating it in vesicle recycling at the synapse. Interestingly, the levels of a fluorescent PI(4,5)P2 reporter are reduced at tweek mutant synapses, and the probe is aberrantly localized during stimulation. In addition, various endocytic adaptors known to bind PI(4,5)P2 are mislocalized and the defects in FM1-43 dye uptake and adaptor localization are partially suppressed by removing one copy of the phosphoinositide phosphatase synaptojanin, suggesting a role for Tweek in maintaining proper phosphoinositide levels at synapses. Our data implicate Tweek in regulating synaptic vesicle recycling via an action mediated at least in part by the regulation of PI(4,5)P2 levels or availability at the synapse.

Original languageEnglish
Pages (from-to)203-215
Number of pages13
Issue number2
StatePublished - Jul 30 2009
Externally publishedYes



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