Dynamics and nanoscale organization of the postsynaptic endocytic zone at excitatory synapses
Abstract
At postsynaptic sites of neurons, a prominent clathrin-coated structure, the endocytic zone (EZ), controls the trafficking of glutamate receptors and is essential for synaptic plasticity. Despite its importance, little is known about how this clathrin structure is organized to mediate endocytosis. We used live-cell and super-resolution microscopy to reveal the dynamic organization of this poorly understood clathrin structure in rat hippocampal neurons. We found that a subset of endocytic proteins only transiently appeared at postsynaptic sites. In contrast, other proteins were persistently enriched and partitioned at the edge of the EZ. We found that uncoupling the EZ from the synapse led to the loss of most of these components, while disrupting interactions with the actin cytoskeleton or membrane did not alter EZ positioning. Finally, we found that plasticity-inducing stimuli promoted the reorganization of the EZ. We conclude that the EZ is a stable, highly organized molecular platform where components are differentially recruited and positioned to orchestrate the endocytosis of synaptic receptors.
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All relevant data are within the paper and its Supporting Information files. All the numerical data that are represented as a graph in a figure are provided in the Source Data file.
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Author details
Funding
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (ALW Open Program grant NWO-ALWOP. 191)
- Harold D MacGillavry
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were performed in compliance with the guidelines for the welfare of experimental animals issued by the Government of the Netherlands (Wet op de Dierproeven, 1996) and European regulations (Guideline 86/609/EEC). All animal experiments were approved by the Dutch Animal Experiments Review Committee (Dier Experimenten Commissie; DEC), performed in line with the institutional guidelines of Utrecht University.
Reviewing Editor
- Eunjoon Kim, Institute for Basic Science, Korea Advanced Institute of Science and Technology, Republic of Korea
Version history
- Preprint posted: February 18, 2021 (view preprint)
- Received: October 4, 2021
- Accepted: November 7, 2021
- Accepted Manuscript published: January 24, 2022 (version 1)
- Version of Record published: February 3, 2022 (version 2)
Copyright
© 2022, Catsburg et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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