RGD Reference Report - Activity-dependent release of tissue plasminogen activator from the dendritic spines of hippocampal neurons revealed by live-cell imaging. - Rat Genome Database

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Activity-dependent release of tissue plasminogen activator from the dendritic spines of hippocampal neurons revealed by live-cell imaging.

Authors: Lochner, Janis E  Honigman, Leah S  Grant, Wilmon F  Gessford, Sarah K  Hansen, Alexis B  Silverman, Michael A  Scalettar, Bethe A 
Citation: Lochner JE, etal., J Neurobiol. 2006 May;66(6):564-77. doi: 10.1002/neu.20250.
RGD ID: 13702316
Pubmed: PMID:16555239   (View Abstract at PubMed)
DOI: DOI:10.1002/neu.20250   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PlatRatglutamatergic synapse is_active_inIDA PMID:16555239SynGO 
PlatRatglutamatergic synapse is_active_inIMP PMID:16555239SynGO 
PlatRatperisynaptic space is_active_inIDA PMID:16555239SynGO 
PlatRatperisynaptic space is_active_inIMP PMID:16555239SynGO 
PlatRatpostsynapse is_active_inIDA PMID:16555239SynGO 
PlatRatpostsynapse is_active_inIMP PMID:16555239SynGO 

Objects Annotated

Genes (Rattus norvegicus)
Plat  (plasminogen activator, tissue type)


Additional Information