Ca2+ and cAMP open differentially dilating synaptic fusion pores.
Dinara Bulgari1, Samantha L Cavolo1, Brigitte F Schmidt2
1Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Journal of Cell Science
|June 12, 2023
Summary
Neuronal dense-core vesicles (DCVs) release cargo via kiss-and-run exocytosis. cAMP signaling opens wider fusion pores, enabling release of larger proteins crucial for synaptic development.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Neuronal dense-core vesicles (DCVs) store neuropeptides and proteins influencing synaptic plasticity.
- DCVs at the Drosophila neuromuscular junction utilize kiss-and-run exocytosis, unlike endocrine cells' full collapse exocytosis.
Purpose of the Study:
- To investigate the permeability range of synaptic DCV fusion pores.
- To understand how larger cargoes are released from DCVs.
- To elucidate the role of cAMP signaling in DCV exocytosis.
Main Methods:
- Fluorogen-activating protein (FAP) imaging to assess fusion pore permeability.
- Investigating Ca2+-independent exocytosis triggered by cAMP.
- Analyzing the roles of PKA-R2, Complexin phosphorylation, and Rugose.
Main Results:
- Synaptic DCV fusion pores have a limited permeability range.
- cAMP-induced extra fusions involve dilating pores, leading to DCV emptying.
- These Ca2+-independent fusions require PKA-R2, Complexin phosphorylation, and Rugose.
Conclusions:
- Localized, Ca2+-independent cAMP signaling opens dilating fusion pores for large cargo release.
- The fusion pore acts as a variable filter, regulating protein composition released at the synapse.
- Distinct exocytosis triggers (Ca2+ for neuropeptide release, cAMP for synaptic development) control cargo composition.
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