AI Article Synopsis
- Synaptic vesicle endocytosis is essential for effective communication at synapses during high activity, and Tweek is a key protein in this process.
- Mutations in the Tweek gene lead to poor FM1-43 dye uptake, larger synaptic vesicles, and impaired neurotransmitter release under intense stimulation.
- Tweek appears to regulate the levels of phosphoinositides like PI(4,5)P(2) at synapses, affecting the localization of important endocytic adaptors, which is critical for proper vesicle recycling.
Article Abstract
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)P(2) 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)P(2) 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)P(2) levels or availability at the synapse.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759194 | PMC |
| http://dx.doi.org/10.1016/j.neuron.2009.06.017 | DOI Listing |
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