Related Experiment Video
Updated: Jan 10, 2026
06:45
In Vivo Single-Molecule Tracking at the Drosophila Presynaptic Motor Nerve Terminal
Published on: January 14, 2018
8.9K
Munc18 modulates syntaxin phase separation to promote exocytosis.
Qing Pei1, Qixin Chen2, Zhiqi Tian2
1Key Laboratory of Cognitive Science, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis & Treatment, Laboratory of Membrane Ion Channels and Medicine, College of Biomedical Engineering, College of Life Sciences, South-Central Minzu University, Wuhan, China.
Nature Neuroscience
|November 25, 2025
Summary
Syntaxin clusters, formed by liquid-liquid phase separation, inhibit neuronal exocytosis and impair mouse behavior. Munc18 binding reduces clustering, promoting efficient fusion.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein syntaxin is crucial for neuronal exocytosis.
- The self-assembly of syntaxin into plasma membrane clusters and their role in synaptic vesicle fusion are not well understood.
Purpose of the Study:
- To investigate the formation and function of syntaxin clusters in regulating neuronal exocytosis.
- To elucidate the mechanism by which syntaxin clustering affects synaptic vesicle fusion and behavior.
Main Methods:
- Utilized optogenetic control for light-inducible syntaxin clustering in vitro and in vivo.
- Investigated cluster formation via liquid-liquid phase separation (LLPS) of the syntaxin SNARE domain.
- Examined the regulatory role of Munc18 in syntaxin clustering and exocytosis.
Main Results:
- Light-enhanced syntaxin clustering reduced both spontaneous and triggered vesicle fusion.
- Syntaxin cluster formation was driven by LLPS of the SNARE domain.
- Munc18 binding decreased LLPS and syntaxin clustering, promoting active syntaxin.
Conclusions:
- Syntaxin clusters, induced by LLPS, act as a reservoir that regulates exocytosis.
- Munc18 captures syntaxin monomers from these clusters to form a complex, facilitating efficient fusion.
- This mechanism highlights the role of LLPS and protein reservoirs in controlling synaptic vesicle release.
Related Concept Videos
01:26Fusion of Secretory Vesicles with the Plasma Membrane
16.5K
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...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
16.5K
01:33Overview of Secretory Vesicles
9.3K
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.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
9.3K
00:50Exocytosis
8.9K
Exocytosis is a process that releases molecules outside the cell. Like other bulk transport mechanisms, exocytosis requires energy.
Exocytosis is the opposite of endocytosis, which brings molecules inside the cell. Sometimes, the released materials are signaling molecules. For example, neurons typically use exocytosis to release neurotransmitters. Cells also use exocytosis to insert proteins such as ion channels into their cell membranes, secrete proteins for use in the extracellular matrix, or...
Exocytosis is the opposite of endocytosis, which brings molecules inside the cell. Sometimes, the released materials are signaling molecules. For example, neurons typically use exocytosis to release neurotransmitters. Cells also use exocytosis to insert proteins such as ion channels into their cell membranes, secrete proteins for use in the extracellular matrix, or...
8.9K
00:51Exocytosis
73.0K
Exocytosis is used to release material from cells. Like other bulk transport mechanisms, exocytosis requires energy.
73.0K
01:43SNAREs and Membrane Fusion
12.3K
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.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
12.3K
01:32Pinching-off of Coated Vesicles
4.0K
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...
4.0K