Cargando…

The Tissue Plasminogen Activator (Tpa/Plasmin) Extracellular Proteolytic System Regulates Seizure-Induced Hippocampal Mossy Fiber Outgrowth through a Proteoglycan Substrate

Short seizure episodes are associated with remodeling of neuronal connections. One region where such reorganization occurs is the hippocampus, and in particular, the mossy fiber pathway. Using genetic and pharmacological approaches, we show here a critical role in vivo for tissue plasminogen activat...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Yan Ping, Siao, Chia-Jen, Lu, Weiquan, Sung, Tsung-Chang, Frohman, Michael A., Milev, Peter, Bugge, Thomas H., Degen, Jay L., Levine, Joel M., Margolis, Richard U., Tsirka, Stella E.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174310/
https://www.ncbi.nlm.nih.gov/pubmed/10725341
_version_ 1782145318253494272
author Wu, Yan Ping
Siao, Chia-Jen
Lu, Weiquan
Sung, Tsung-Chang
Frohman, Michael A.
Milev, Peter
Bugge, Thomas H.
Degen, Jay L.
Levine, Joel M.
Margolis, Richard U.
Tsirka, Stella E.
author_facet Wu, Yan Ping
Siao, Chia-Jen
Lu, Weiquan
Sung, Tsung-Chang
Frohman, Michael A.
Milev, Peter
Bugge, Thomas H.
Degen, Jay L.
Levine, Joel M.
Margolis, Richard U.
Tsirka, Stella E.
author_sort Wu, Yan Ping
collection PubMed
description Short seizure episodes are associated with remodeling of neuronal connections. One region where such reorganization occurs is the hippocampus, and in particular, the mossy fiber pathway. Using genetic and pharmacological approaches, we show here a critical role in vivo for tissue plasminogen activator (tPA), an extracellular protease that converts plasminogen to plasmin, to induce mossy fiber sprouting. We identify DSD-1-PG/phosphacan, an extracellular matrix component associated with neurite reorganization, as a physiological target of plasmin. Mice lacking tPA displayed decreased mossy fiber outgrowth and an aberrant band at the border of the supragranular region of the dentate gyrus that coincides with the deposition of unprocessed DSD-1-PG/phosphacan and excessive Timm-positive, mossy fiber termini. Plasminogen-deficient mice also exhibit the laminar band and DSD- 1-PG/phosphacan deposition, but mossy fiber outgrowth through the supragranular region is normal. These results demonstrate that tPA functions acutely, both through and independently of plasmin, to mediate mossy fiber reorganization.
format Text
id pubmed-2174310
institution National Center for Biotechnology Information
language English
publishDate 2000
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21743102008-05-01 The Tissue Plasminogen Activator (Tpa/Plasmin) Extracellular Proteolytic System Regulates Seizure-Induced Hippocampal Mossy Fiber Outgrowth through a Proteoglycan Substrate Wu, Yan Ping Siao, Chia-Jen Lu, Weiquan Sung, Tsung-Chang Frohman, Michael A. Milev, Peter Bugge, Thomas H. Degen, Jay L. Levine, Joel M. Margolis, Richard U. Tsirka, Stella E. J Cell Biol Original Article Short seizure episodes are associated with remodeling of neuronal connections. One region where such reorganization occurs is the hippocampus, and in particular, the mossy fiber pathway. Using genetic and pharmacological approaches, we show here a critical role in vivo for tissue plasminogen activator (tPA), an extracellular protease that converts plasminogen to plasmin, to induce mossy fiber sprouting. We identify DSD-1-PG/phosphacan, an extracellular matrix component associated with neurite reorganization, as a physiological target of plasmin. Mice lacking tPA displayed decreased mossy fiber outgrowth and an aberrant band at the border of the supragranular region of the dentate gyrus that coincides with the deposition of unprocessed DSD-1-PG/phosphacan and excessive Timm-positive, mossy fiber termini. Plasminogen-deficient mice also exhibit the laminar band and DSD- 1-PG/phosphacan deposition, but mossy fiber outgrowth through the supragranular region is normal. These results demonstrate that tPA functions acutely, both through and independently of plasmin, to mediate mossy fiber reorganization. The Rockefeller University Press 2000-03-20 /pmc/articles/PMC2174310/ /pubmed/10725341 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Wu, Yan Ping
Siao, Chia-Jen
Lu, Weiquan
Sung, Tsung-Chang
Frohman, Michael A.
Milev, Peter
Bugge, Thomas H.
Degen, Jay L.
Levine, Joel M.
Margolis, Richard U.
Tsirka, Stella E.
The Tissue Plasminogen Activator (Tpa/Plasmin) Extracellular Proteolytic System Regulates Seizure-Induced Hippocampal Mossy Fiber Outgrowth through a Proteoglycan Substrate
title The Tissue Plasminogen Activator (Tpa/Plasmin) Extracellular Proteolytic System Regulates Seizure-Induced Hippocampal Mossy Fiber Outgrowth through a Proteoglycan Substrate
title_full The Tissue Plasminogen Activator (Tpa/Plasmin) Extracellular Proteolytic System Regulates Seizure-Induced Hippocampal Mossy Fiber Outgrowth through a Proteoglycan Substrate
title_fullStr The Tissue Plasminogen Activator (Tpa/Plasmin) Extracellular Proteolytic System Regulates Seizure-Induced Hippocampal Mossy Fiber Outgrowth through a Proteoglycan Substrate
title_full_unstemmed The Tissue Plasminogen Activator (Tpa/Plasmin) Extracellular Proteolytic System Regulates Seizure-Induced Hippocampal Mossy Fiber Outgrowth through a Proteoglycan Substrate
title_short The Tissue Plasminogen Activator (Tpa/Plasmin) Extracellular Proteolytic System Regulates Seizure-Induced Hippocampal Mossy Fiber Outgrowth through a Proteoglycan Substrate
title_sort tissue plasminogen activator (tpa/plasmin) extracellular proteolytic system regulates seizure-induced hippocampal mossy fiber outgrowth through a proteoglycan substrate
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174310/
https://www.ncbi.nlm.nih.gov/pubmed/10725341
work_keys_str_mv AT wuyanping thetissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT siaochiajen thetissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT luweiquan thetissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT sungtsungchang thetissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT frohmanmichaela thetissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT milevpeter thetissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT buggethomash thetissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT degenjayl thetissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT levinejoelm thetissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT margolisrichardu thetissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT tsirkastellae thetissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT wuyanping tissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT siaochiajen tissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT luweiquan tissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT sungtsungchang tissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT frohmanmichaela tissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT milevpeter tissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT buggethomash tissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT degenjayl tissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT levinejoelm tissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT margolisrichardu tissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate
AT tsirkastellae tissueplasminogenactivatortpaplasminextracellularproteolyticsystemregulatesseizureinducedhippocampalmossyfiberoutgrowththroughaproteoglycansubstrate