Two-Chains Tissue Plasminogen Activator Unifies Met and NMDA Receptor Signalling to Control Neuronal Survival
Tissue-type plasminogen activator (tPA) plays roles in the development and the plasticity of the nervous system. Here, we demonstrate in neurons, that by opposition to the single chain form (sc-tPA), the two-chains form of tPA (tc-tPA) activates the MET receptor, leading to the recruitment of -Methy...
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| Veröffentlicht in: | International journal of molecular sciences 2021-12, Vol.22 (24), p.13483 |
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| creator | Hedou, Elodie Douceau, Sara Chevilley, Arnaud Varangot, Alexandre Thiebaut, Audrey M Triniac, Hortense Bardou, Isabelle Ali, Carine Maillasson, Mike Crepaldi, Tiziana Comoglio, Paolo Lemarchand, Eloïse Agin, Véronique Roussel, Benoit D Vivien, Denis |
| description | Tissue-type plasminogen activator (tPA) plays roles in the development and the plasticity of the nervous system. Here, we demonstrate in neurons, that by opposition to the single chain form (sc-tPA), the two-chains form of tPA (tc-tPA) activates the MET receptor, leading to the recruitment of
-Methyl-d-Aspartate receptors (NMDARs) and to the endocytosis and proteasome-dependent degradation of NMDARs containing the GluN2B subunit. Accordingly, tc-tPA down-regulated GluN2B-NMDAR-driven signalling, a process prevented by blockers of HGFR/MET and mimicked by its agonists, leading to a modulation of neuronal death. Thus, our present study unmasks a new mechanism of action of tPA, with its two-chains form mediating a crosstalk between MET and the GluN2B subunit of NMDARs to control neuronal survival. |
| doi_str_mv | 10.3390/ijms222413483 |
| format | Article |
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-Methyl-d-Aspartate receptors (NMDARs) and to the endocytosis and proteasome-dependent degradation of NMDARs containing the GluN2B subunit. Accordingly, tc-tPA down-regulated GluN2B-NMDAR-driven signalling, a process prevented by blockers of HGFR/MET and mimicked by its agonists, leading to a modulation of neuronal death. Thus, our present study unmasks a new mechanism of action of tPA, with its two-chains form mediating a crosstalk between MET and the GluN2B subunit of NMDARs to control neuronal survival.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms222413483</identifier><identifier>PMID: 34948279</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Cancer ; Cell Death - drug effects ; Cell Survival - drug effects ; Chains ; Crosstalk ; Developmental plasticity ; Endocytosis ; Experiments ; Fetus ; Glutamate receptors ; Glutamic acid receptors (ionotropic) ; Life Sciences ; Mice ; N-Methyl-D-aspartic acid receptors ; Nervous system ; Neuromodulation ; Neurons - metabolism ; Phosphorylation ; Primary Cell Culture ; Proteasomes ; Protein Isoforms ; Proto-Oncogene Proteins c-met - metabolism ; Proto-Oncogene Proteins c-met - physiology ; Receptor Cross-Talk - physiology ; Receptors, N-Methyl-D-Aspartate - metabolism ; Signal Transduction ; Survival ; t-Plasminogen activator ; Thrombolytic drugs ; Tissue Plasminogen Activator - metabolism ; Tissue Plasminogen Activator - physiology</subject><ispartof>International journal of molecular sciences, 2021-12, Vol.22 (24), p.13483</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-eca7a316f390ef7216822b72c8c7bc4f40b559c73227ba1ac68708e2268d3b613</citedby><cites>FETCH-LOGICAL-c452t-eca7a316f390ef7216822b72c8c7bc4f40b559c73227ba1ac68708e2268d3b613</cites><orcidid>0000-0001-9526-7880 ; 0000-0003-0575-8112 ; 0000-0003-4971-3987 ; 0000-0003-3410-947X ; 0000-0002-0144-6106</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707453/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707453/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34948279$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-03547069$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Hedou, Elodie</creatorcontrib><creatorcontrib>Douceau, Sara</creatorcontrib><creatorcontrib>Chevilley, Arnaud</creatorcontrib><creatorcontrib>Varangot, Alexandre</creatorcontrib><creatorcontrib>Thiebaut, Audrey M</creatorcontrib><creatorcontrib>Triniac, Hortense</creatorcontrib><creatorcontrib>Bardou, Isabelle</creatorcontrib><creatorcontrib>Ali, Carine</creatorcontrib><creatorcontrib>Maillasson, Mike</creatorcontrib><creatorcontrib>Crepaldi, Tiziana</creatorcontrib><creatorcontrib>Comoglio, Paolo</creatorcontrib><creatorcontrib>Lemarchand, Eloïse</creatorcontrib><creatorcontrib>Agin, Véronique</creatorcontrib><creatorcontrib>Roussel, Benoit D</creatorcontrib><creatorcontrib>Vivien, Denis</creatorcontrib><title>Two-Chains Tissue Plasminogen Activator Unifies Met and NMDA Receptor Signalling to Control Neuronal Survival</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Tissue-type plasminogen activator (tPA) plays roles in the development and the plasticity of the nervous system. Here, we demonstrate in neurons, that by opposition to the single chain form (sc-tPA), the two-chains form of tPA (tc-tPA) activates the MET receptor, leading to the recruitment of
-Methyl-d-Aspartate receptors (NMDARs) and to the endocytosis and proteasome-dependent degradation of NMDARs containing the GluN2B subunit. Accordingly, tc-tPA down-regulated GluN2B-NMDAR-driven signalling, a process prevented by blockers of HGFR/MET and mimicked by its agonists, leading to a modulation of neuronal death. 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Here, we demonstrate in neurons, that by opposition to the single chain form (sc-tPA), the two-chains form of tPA (tc-tPA) activates the MET receptor, leading to the recruitment of
-Methyl-d-Aspartate receptors (NMDARs) and to the endocytosis and proteasome-dependent degradation of NMDARs containing the GluN2B subunit. Accordingly, tc-tPA down-regulated GluN2B-NMDAR-driven signalling, a process prevented by blockers of HGFR/MET and mimicked by its agonists, leading to a modulation of neuronal death. Thus, our present study unmasks a new mechanism of action of tPA, with its two-chains form mediating a crosstalk between MET and the GluN2B subunit of NMDARs to control neuronal survival.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>34948279</pmid><doi>10.3390/ijms222413483</doi><orcidid>https://orcid.org/0000-0001-9526-7880</orcidid><orcidid>https://orcid.org/0000-0003-0575-8112</orcidid><orcidid>https://orcid.org/0000-0003-4971-3987</orcidid><orcidid>https://orcid.org/0000-0003-3410-947X</orcidid><orcidid>https://orcid.org/0000-0002-0144-6106</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2021-12, Vol.22 (24), p.13483 |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Cancer Cell Death - drug effects Cell Survival - drug effects Chains Crosstalk Developmental plasticity Endocytosis Experiments Fetus Glutamate receptors Glutamic acid receptors (ionotropic) Life Sciences Mice N-Methyl-D-aspartic acid receptors Nervous system Neuromodulation Neurons - metabolism Phosphorylation Primary Cell Culture Proteasomes Protein Isoforms Proto-Oncogene Proteins c-met - metabolism Proto-Oncogene Proteins c-met - physiology Receptor Cross-Talk - physiology Receptors, N-Methyl-D-Aspartate - metabolism Signal Transduction Survival t-Plasminogen activator Thrombolytic drugs Tissue Plasminogen Activator - metabolism Tissue Plasminogen Activator - physiology |
| title | Two-Chains Tissue Plasminogen Activator Unifies Met and NMDA Receptor Signalling to Control Neuronal Survival |
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