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Related Concept Videos

Fusion of Secretory Vesicles with the Plasma Membrane01:26

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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.
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After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
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SNAREs and Membrane Fusion01:43

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Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
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Intralumenal Vesicles and Multivesicular Bodies01:38

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Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
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Overview of Secretory Vesicles01:33

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Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
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Rab Cascades01:25

Rab Cascades

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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.
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Examination of Synaptic Vesicle Recycling Using FM Dyes During Evoked, Spontaneous, and Miniature Synaptic Activities
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Simultaneous Release of Multiple Vesicles from Rods Involves Synaptic Ribbons and Syntaxin 3B.

Cassandra L Hays1, Justin J Grassmeyer2, Xiangyi Wen3

  • 1Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska; Department of Ophthalmology and Visual Sciences, Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska.

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Summary

Multivesicular release, where multiple vesicles release neurotransmitters simultaneously, is common in the brain. In retinal rod photoreceptors, this process at ribbon synapses requires functional ribbons and involves syntaxin 3B, suggesting vesicle fusion.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Synaptic Transmission

Background:

  • Multivesicular release, initially observed in sensory neurons, is now recognized throughout the central nervous system.
  • Despite its prevalence, the precise mechanisms governing multivesicular release remain incompletely understood.
  • Ribbon synapses in retinal photoreceptors are critical for visual processing and exhibit specialized release properties.

Purpose of the Study:

  • To investigate the mechanisms underlying simultaneous multivesicular release at ribbon synapses in salamander retinal rod photoreceptors.
  • To determine the contribution of multiquantal events to spontaneous neurotransmitter release.
  • To elucidate the role of synaptic ribbons and specific proteins in regulating multivesicular release.

Main Methods:

  • Presynaptic recordings of glutamate transporter anion currents (IA(glu)) in rod photoreceptors.
  • Simultaneous postsynaptic recordings of miniature excitatory postsynaptic currents (mEPSCs) in horizontal cells.
  • Application of calcium buffers, photoinactivation of synaptic ribbons, and interference with syntaxin 3B.

Main Results:

  • Approximately 30% of spontaneous release events were multiquantal, with larger events correlating with greater glutamate release.
  • The highly synchronized release of multiple vesicles during multiquantal events was confirmed by identical kinetics.
  • Spontaneous multiquantal release was dependent on functional synaptic ribbons and involved syntaxin 3B, suggesting homotypic vesicle fusion.

Conclusions:

  • Simultaneous multiquantal release at ribbon synapses in rod photoreceptors is a significant mode of spontaneous neurotransmission.
  • Functional synaptic ribbons and the SNARE protein syntaxin 3B are crucial for this process.
  • Evoked and spontaneous multiquantal release appear to utilize distinct vesicle pools.