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A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
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Synaptic activity regulates AMPA receptor trafficking through different recycling pathways.
Ning Zheng1, Okunola Jeyifous1, Charlotte Munro2
1Department of Neurobiology, University of Chicago, Chicago, United States.
Elife
|May 14, 2015
Summary
AMPA receptor recycling in the brain involves distinct pathways regulated by synaptic activity. Arf6 GTPase mediates recycling without stimulation, while dynamin-dependent pathways become active during synaptic plasticity.
Area of Science:
- Neuroscience
- Cell Biology
- Synaptic Plasticity
Background:
- Glutamatergic synaptic strength relies on AMPA-type glutamate receptor (AMPAR) recycling.
- Current understanding assumes a single, local pathway for AMPAR recycling.
Purpose of the Study:
- To investigate if AMPAR recycling occurs through multiple pathways.
- To determine the role of synaptic activity in regulating AMPAR recycling pathways.
Main Methods:
- Investigated AMPAR recycling using dynamin-independent (Arf6-containing) and dynamin-dependent (transferrin receptor-labeled) endosomes.
- Utilized GTPase TC10 alterations and mutants to assess effects on AMPAR recycling.
- Examined AMPAR levels during long-term potentiation (LTP) and long-term depression (LTD).
Main Results:
- Without stimulation, AMPARs primarily recycled via Arf6-dependent endosomes.
- TC10 GTPase, co-localizing with Arf6, regulates AMPAR recycling.
- LTP increased AMPAR internalization in TfR-containing endosomes, indicating enhanced dynamin-dependent recycling.
- TC10 mutants affected basal recycling but not LTP/LTD-induced changes in surface AMPARs.
Conclusions:
- AMPAR recycling is not limited to a single pathway but is modulated by synaptic activity.
- Distinct pathways, involving Arf6 and dynamin, handle AMPAR recycling under different conditions.
- LTP-induced increases in surface AMPARs may involve trafficking from extralocal sources, challenging the local recycling model.
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