Related Experiment Video
Updated: Jul 17, 2026
09:33
An Optical Assay for Synaptic Vesicle Recycling in Cultured Neurons Overexpressing Presynaptic Proteins
Published on: June 26, 2018
Dvl regulates endo- and exocytotic processes through binding to synaptotagmin
Shosei Kishida1, Kozue Hamao, Makoto Inoue
1Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|January 11, 2007
Summary
Dishevelled (Dvl) regulates neurotransmitter release by binding to synaptotagmin I (Syt I). This interaction influences both the exocytosis and endocytosis of dopamine-containing vesicles, impacting neuronal communication.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Dishevelled (Dvl) is a key Wnt signaling pathway component implicated in synaptogenesis.
- The precise role of Dvl in regulating neurotransmitter release remains largely unexplored.
Purpose of the Study:
- To investigate the role of Dvl in regulating neurotransmitter release.
- To identify proteins interacting with Dvl that are involved in neurotransmitter release.
Main Methods:
- PC12 cell culture and differentiation.
- Dvl knockdown and rescue experiments.
- Co-immunoprecipitation and Western blotting to identify protein interactions.
- Immunofluorescence microscopy to determine protein localization.
- Analysis of vesicle endocytosis and exocytosis.
Main Results:
- Dvl knockdown in PC12 cells suppressed K(+)-induced dopamine release.
- Synaptotagmin I (Syt I) was identified as a Dvl-binding protein, interacting with Dvl's C2B domain.
- Dvl and Syt I colocalized at neurite tips and within dopamine-containing large dense-core vesicles.
- Dvl knockdown suppressed Syt I-containing vesicle endocytosis and inhibited Syt I binding to syntaxin-1A/SNAP-25 complex.
- Dvl formed a complex with Syt I and micro2-adaptin of AP-2, suggesting a role in endocytosis.
Conclusions:
- Dvl plays a critical role in regulating neurotransmitter release, specifically dopamine.
- Dvl interacts with Syt I to modulate both exocytotic and endocytotic processes involving synaptic vesicles.
- These findings reveal a novel function of Dvl in synaptic vesicle trafficking and neurotransmission.
Related Concept Videos
01:26Fusion of Secretory Vesicles with the Plasma Membrane
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...
01:43SNAREs and Membrane Fusion
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...
01:33Overview of Secretory Vesicles
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...
01:32Pinching-off of Coated Vesicles
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...
01:12Clathrin Coated Vesicles
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...
01:38Intralumenal Vesicles and Multivesicular Bodies
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...