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Plasminogen trafficks through the regulated secretory pathway in hippocampal neurons
Author(s) -
Chavarha Mariya,
Jacobs Conor,
McAllister Kevin,
Scalletar Bethe A,
Lochner Janis E
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.800.2
Subject(s) - hippocampal formation , soma , neuroscience , microbiology and biotechnology , chemistry , biology
Plasminogen has emerged as a key player in learning and memory and neurodegeneration in the hippocampus, and yet little is known about its localization or secretory trafficking to synaptic sites in hippocampal neurons. To address these issues, we constructed a fluorescent chimeric protein, plasminogen‐mCherry, to facilitate a study of the packaging, transport, and synaptic localization of plasminogen in cultured hippocampal neurons. Our results indicate that the plasminogen chimera localizes to regions of the soma typically occupied by the Golgi and to spherical organelles that are distributed throughout the soma and processes. We find 82% co‐localization of puncta containing plasminogen chimeras with markers for dense‐core granules (DCGs), suggesting that secretion of plasminogen from hippocampal neurons is regulated. Plasminogen chimeras were found, co‐localized with the neuromodulatory protein pro‐brain derived neurotrophic factor (proBDNF), within DCGs at post‐synaptic sites. These results demonstrate that plasminogen is co‐packaged with proBDNF and traffics through the regulated secretory pathway of hippocampal neurons to post‐synaptic sites where it is strategically positioned to undergo co‐release with other neuromodulatory proteins. This work was supported by National Institutes of Health grants 2 R15 NS40425‐02 and 2 R15 GM061539‐02.