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Two-photon Calcium Imaging in Neuronal Dendrites in Brain Slices
Published on: March 15, 2018
Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release.
Alexander J Groffen1, Sascha Martens, Rocío Díez Arazola
1Department of Functional Genomics, CNCR, Neuroscience Campus Amsterdam, VU University and VU Medical Center, Amsterdam, 1081 HV, Netherlands. sander.groffen@cncr.vu.nl
Science (New York, N.Y.)
|February 13, 2010
Summary
Double C2 (Doc2) proteins are calcium sensors that trigger spontaneous neurotransmitter release. They compete with synaptotagmin proteins, suggesting a dual mechanism for synaptic vesicle fusion.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Synaptic vesicle fusion underlies neurotransmission, occurring synchronously or spontaneously.
- Synaptotagmin proteins (Syt1, Syt2, Syt9) are known Ca2+ sensors for synchronous release.
- Spontaneous release, crucial for basal synaptic function, requires distinct Ca2+ sensing mechanisms.
Purpose of the Study:
- To identify the Ca2+ sensors responsible for spontaneous synaptic vesicle fusion.
- To elucidate the mechanism by which these sensors regulate spontaneous release.
- To compare the function of spontaneous release sensors with those of synchronous release.
Main Methods:
- Biochemical assays to assess protein-protein interactions.
- Calcium titration experiments to determine Ca2+ sensitivity.
- In vitro reconstitution of synaptic vesicle fusion.
Main Results:
- Double C2 (Doc2) proteins function as Ca2+ sensors for spontaneous vesicle fusion.
- Doc2 proteins exhibit higher Ca2+ sensitivity compared to synaptotagmins.
- Doc2 proteins bind to SNARE complexes, competing with synaptotagmin-1.
Conclusions:
- Doc2 proteins are key regulators of spontaneous neurotransmitter release.
- Distinct C2 domain-containing proteins (Syt vs. Doc2) mediate different fusion phases.
- A general model for Ca2+-triggered synaptic vesicle fusion involves SNAREs and C2 domain proteins.
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