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.
Highlights
Clathrin-mediated endocytosis is the principal mechanism for the internalization of membrane components, and is essential for cellular homeostasis, intercellular signaling and nutrient uptake in mammalian cells (Kaksonen and Roux, 2018; McMahon and Boucrot, 2011; Mettlen et al, 2018)
We found that 59 ± 5% of the postsynaptic density (PSD) were associated with one clathrin structure, while 14 ± 2% and 5.4 ± 0.8%
We found that the centroid of the endocytic zone (EZ) was generally located within 100 nm from the border of the PSD
Summary
Clathrin-mediated endocytosis is the principal mechanism for the internalization of membrane components, and is essential for cellular homeostasis, intercellular signaling and nutrient uptake in mammalian cells (Kaksonen and Roux, 2018; McMahon and Boucrot, 2011; Mettlen et al, 2018). This process involves the tightlycontrolled initiation and maturation of clathrin-coated pits that is mediated by the sequential recruitment of clathrin, cargo and endocytic adaptor proteins (Cocucci et al, 2012; Taylor et al, 2011). The origins and functional relevance of this striking heterogeneity remain to be elucidated
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