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Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

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Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
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Clathrin Coated Vesicles01:12

Clathrin Coated Vesicles

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Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
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Fusion of Secretory Vesicles with the Plasma Membrane01:26

Fusion of Secretory Vesicles with the Plasma Membrane

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Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
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Coat Assembly and GTPases01:33

Coat Assembly and GTPases

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Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
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Rab Cascades01:25

Rab Cascades

2.6K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
2.6K
Long-term Potentiation01:25

Long-term Potentiation

2.7K
Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
Hebbian LTP
LTP can occur when...
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Related Experiment Video

Updated: May 17, 2025

An Optical Assay for Synaptic Vesicle Recycling in Cultured Neurons Overexpressing Presynaptic Proteins
09:33

An Optical Assay for Synaptic Vesicle Recycling in Cultured Neurons Overexpressing Presynaptic Proteins

Published on: June 26, 2018

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Power-law adaptation in the presynaptic vesicle cycle.

Fabian A Mikulasch1, Svilen V Georgiev2,3, Lucas Rudelt1,4

  • 1Max-Planck-Institute for Dynamics and Self-Organization, Göttingen, Germany.

Communications Biology
|April 2, 2025
PubMed
Summary

Synaptic vesicle recycling dynamics involve multiple timescales, impacting neuronal communication. This study models and experimentally validates these dynamics, revealing how synaptic adaptation enables efficient neural signal processing in the hippocampus.

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Measuring Synaptic Vesicle Endocytosis in Cultured Hippocampal Neurons
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Related Experiment Videos

Last Updated: May 17, 2025

An Optical Assay for Synaptic Vesicle Recycling in Cultured Neurons Overexpressing Presynaptic Proteins
09:33

An Optical Assay for Synaptic Vesicle Recycling in Cultured Neurons Overexpressing Presynaptic Proteins

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Measuring Membrane Lipid Turnover with the pH-sensitive Fluorescent Lipid Analog ND6
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Measuring Membrane Lipid Turnover with the pH-sensitive Fluorescent Lipid Analog ND6

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Area of Science:

  • Neuroscience
  • Computational Biology
  • Cellular Biology

Background:

  • Synaptic transmission relies on the recycling of synaptic vesicles to maintain neuronal function.
  • Individual steps of vesicle recycling (endocytosis, docking, priming) are understood, but their collective impact on synaptic dynamics and signal transmission remains unclear.

Purpose of the Study:

  • To model the dynamics of synaptic vesicle recycling and understand its influence on overall synaptic recovery and signal transmission.
  • To investigate the functional implications of multi-timescale synaptic dynamics in neural circuits.

Main Methods:

  • Developed a mathematical model for synaptic vesicle recycling dynamics, incorporating multiple timescales.
  • Experimentally validated the model using cultured hippocampal neurons.
  • Analyzed the impact of synaptic exhaustion duration on synaptic recovery timescales.

Main Results:

  • The study found that multiple timescales of recycling steps are reflected in synaptic recovery, leading to multi-timescale synapse dynamics.
  • A simplified synaptic model with 'power-law' adaptation accurately describes these dynamics.
  • Experimental results confirmed that synaptic exhaustion duration alters the effective synaptic recovery timescale, consistent with the model's predictions.

Conclusions:

  • Synaptic vesicle recycling exhibits multi-timescale dynamics that influence synaptic recovery and signal transmission.
  • The 'power-law' adaptation model provides a framework for understanding these complex dynamics.
  • This synaptic adaptation mechanism may facilitate efficient neuronal communication in the hippocampus by temporally whitening spike trains.