Source:http://linkedlifedata.com/resource/pubmed/id/16555239
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2006-4-12
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| pubmed:abstractText |
Tissue plasminogen activator (tPA) has been implicated in a variety of important cellular functions, including learning-related synaptic plasticity and potentiating N-methyl-D-aspartate (NMDA) receptor-dependent signaling. These findings suggest that tPA may localize to, and undergo activity-dependent secretion from, synapses; however, conclusive data supporting these hypotheses have remained elusive. To elucidate these issues, we studied the distribution, dynamics, and depolarization-induced secretion of tPA in hippocampal neurons, using fluorescent chimeras of tPA. We found that tPA resides in dense-core granules (DCGs) that traffic to postsynaptic dendritic spines and that can remain in spines for extended periods. We also found that depolarization induced by high potassium levels elicits a slow, partial exocytotic release of tPA from DCGs in spines that is dependent on extracellular Ca(+2) concentrations. This slow, partial release demonstrates that exocytosis occurs via a mechanism, such as fuse-pinch-linger, that allows partial release and reuse of DCG cargo and suggests a mechanism that hippocampal neurons may rely upon to avoid depleting tPA at active synapses. Our results also demonstrate release of tPA at a site that facilitates interaction with NMDA-type glutamate receptors, and they provide direct confirmation of fundamental hypotheses about tPA localization and release that bear on its neuromodulatory functions, for example, in learning and memory.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mutant Chimeric Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Plasminogen Activator,
http://linkedlifedata.com/resource/pubmed/chemical/yellow fluorescent protein, Bacteria
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
0022-3034
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
66
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
564-77
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| pubmed:dateRevised |
2007-12-3
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| pubmed:meshHeading |
pubmed-meshheading:16555239-Animals,
pubmed-meshheading:16555239-Bacterial Proteins,
pubmed-meshheading:16555239-Calcium Signaling,
pubmed-meshheading:16555239-Cells, Cultured,
pubmed-meshheading:16555239-Dendritic Spines,
pubmed-meshheading:16555239-Exocytosis,
pubmed-meshheading:16555239-Hippocampus,
pubmed-meshheading:16555239-Luminescent Proteins,
pubmed-meshheading:16555239-Membrane Potentials,
pubmed-meshheading:16555239-Memory,
pubmed-meshheading:16555239-Microscopy, Fluorescence,
pubmed-meshheading:16555239-Microscopy, Video,
pubmed-meshheading:16555239-Mutant Chimeric Proteins,
pubmed-meshheading:16555239-Potassium,
pubmed-meshheading:16555239-Protein Transport,
pubmed-meshheading:16555239-Pyramidal Cells,
pubmed-meshheading:16555239-Rats,
pubmed-meshheading:16555239-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:16555239-Secretory Vesicles,
pubmed-meshheading:16555239-Synaptic Transmission,
pubmed-meshheading:16555239-Time Factors,
pubmed-meshheading:16555239-Tissue Plasminogen Activator
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| pubmed:year |
2006
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| pubmed:articleTitle |
Activity-dependent release of tissue plasminogen activator from the dendritic spines of hippocampal neurons revealed by live-cell imaging.
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| pubmed:affiliation |
Department of Chemistry, Lewis & Clark College, Portland, OR 97219, USA. Lochner@LClark.edu
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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