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Updated: Jul 4, 2026
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An Optical Assay for Synaptic Vesicle Recycling in Cultured Neurons Overexpressing Presynaptic Proteins
Published on: June 26, 2018
Efficient copackaging and cotransport yields postsynaptic colocalization of neuromodulators associated with synaptic
J E Lochner1, E Spangler, M Chavarha
1Department of Chemistry, Lewis & Clark College, Portland, Oregon 97219, USA.
Developmental Neurobiology
|June 20, 2008
Summary
Tissue plasminogen activator (tPA) and its related proteins are packaged together in dense-core granules within hippocampal neurons. These granules are transported to dendritic spines, suggesting a mechanism for synaptic plasticity.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Tissue plasminogen activator (tPA) is implicated in long-term synaptic plasticity.
- tPA converts plasminogen to plasmin, generating mature brain-derived neurotrophic factor (mBDNF) from its precursor, proBDNF.
Purpose of the Study:
- Investigate plasminogen secretion mechanisms in hippocampal neurons.
- Determine if tPA, plasminogen, and proBDNF are co-packaged and co-transported.
- Elucidate transport mechanisms of these neuromodulators to release sites.
Main Methods:
- Utilized fluorescent chimeras expressed in hippocampal neurons.
- Examined trafficking through the regulated secretory pathway and dense-core granules (DCGs).
- Analyzed co-localization within DCGs, particularly in dendritic spines.
Main Results:
- Plasminogen traffics via the regulated secretory pathway in DCGs.
- tPA, plasminogen, and proBDNF are extensively co-packaged within DCGs.
- 80% of spines with DCGs contain these neuromodulators within the same granule.
- Neuromodulators are co-transported in rapidly mobile DCGs along dendrites.
Conclusions:
- Results support the hypothesis that tPA mediates synaptic BDNF activation.
- tPA, plasminogen, and proBDNF co-localize in DCGs within spines for activity-dependent release.
- Neuromodulator release from DCGs may influence synaptic plasticity direction by altering mBDNF/proBDNF ratios.
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