Evidence of Presynaptic Localization and Function of the c-Jun N-Terminal Kinase
The c-Jun N-terminal kinase (JNK) is part of a stress signalling pathway strongly activated by NMDA-stimulation and involved in synaptic plasticity. Many studies have been focused on the post-synaptic mechanism of JNK action, and less is known about JNK presynaptic localization and its physiological...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2017/6468356 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832562696175747072 |
|---|---|
| author | Silvia Biggi Lucia Buccarello Alessandra Sclip Pellegrino Lippiello Noemi Tonna Cristiano Rumio Daniele Di Marino Maria Concetta Miniaci Tiziana Borsello |
| author_facet | Silvia Biggi Lucia Buccarello Alessandra Sclip Pellegrino Lippiello Noemi Tonna Cristiano Rumio Daniele Di Marino Maria Concetta Miniaci Tiziana Borsello |
| author_sort | Silvia Biggi |
| collection | DOAJ |
| description | The c-Jun N-terminal kinase (JNK) is part of a stress signalling pathway strongly activated by NMDA-stimulation and involved in synaptic plasticity. Many studies have been focused on the post-synaptic mechanism of JNK action, and less is known about JNK presynaptic localization and its physiological role at this site. Here we examined whether JNK is present at the presynaptic site and its activity after presynaptic NMDA receptors stimulation. By using N-SIM Structured Super Resolution Microscopy as well as biochemical approaches, we demonstrated that presynaptic fractions contained significant amount of JNK protein and its activated form. By means of modelling design, we found that JNK, via the JBD domain, acts as a physiological effector on T-SNARE proteins; then using biochemical approaches we demonstrated the interaction between Syntaxin-1-JNK, Syntaxin-2-JNK, and Snap25-JNK. In addition, taking advance of the specific JNK inhibitor peptide, D-JNKI1, we defined JNK action on the SNARE complex formation. Finally, electrophysiological recordings confirmed the role of JNK in the presynaptic modulation of vesicle release. These data suggest that JNK-dependent phosphorylation of T-SNARE proteins may have an important functional role in synaptic plasticity. |
| format | Article |
| id | doaj-art-bdb85762c50a4431b3d7a5fde5955af7 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-bdb85762c50a4431b3d7a5fde5955af72025-02-03T01:22:01ZengWileyNeural Plasticity2090-59041687-54432017-01-01201710.1155/2017/64683566468356Evidence of Presynaptic Localization and Function of the c-Jun N-Terminal KinaseSilvia Biggi0Lucia Buccarello1Alessandra Sclip2Pellegrino Lippiello3Noemi Tonna4Cristiano Rumio5Daniele Di Marino6Maria Concetta Miniaci7Tiziana Borsello8IRCCS Istituto di Ricerche Farmacologiche “Mario Negri”, Via La Masa 19, 20156 Milano, ItalyIRCCS Istituto di Ricerche Farmacologiche “Mario Negri”, Via La Masa 19, 20156 Milano, ItalyIRCCS Istituto di Ricerche Farmacologiche “Mario Negri”, Via La Masa 19, 20156 Milano, ItalyDepartment of Pharmacy, University of Naples Federico II, Naples, ItalySanipedia S.r.l., Via Ariosto 21, 20091 Bresso, ItalyDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milano, ItalyDepartment of Informatics, Institute of Computational Science, Università della Svizzera Italiana (USI), Via G. Bu 13, 6900 Lugano, SwitzerlandDepartment of Pharmacy, University of Naples Federico II, Naples, ItalyIRCCS Istituto di Ricerche Farmacologiche “Mario Negri”, Via La Masa 19, 20156 Milano, ItalyThe c-Jun N-terminal kinase (JNK) is part of a stress signalling pathway strongly activated by NMDA-stimulation and involved in synaptic plasticity. Many studies have been focused on the post-synaptic mechanism of JNK action, and less is known about JNK presynaptic localization and its physiological role at this site. Here we examined whether JNK is present at the presynaptic site and its activity after presynaptic NMDA receptors stimulation. By using N-SIM Structured Super Resolution Microscopy as well as biochemical approaches, we demonstrated that presynaptic fractions contained significant amount of JNK protein and its activated form. By means of modelling design, we found that JNK, via the JBD domain, acts as a physiological effector on T-SNARE proteins; then using biochemical approaches we demonstrated the interaction between Syntaxin-1-JNK, Syntaxin-2-JNK, and Snap25-JNK. In addition, taking advance of the specific JNK inhibitor peptide, D-JNKI1, we defined JNK action on the SNARE complex formation. Finally, electrophysiological recordings confirmed the role of JNK in the presynaptic modulation of vesicle release. These data suggest that JNK-dependent phosphorylation of T-SNARE proteins may have an important functional role in synaptic plasticity.http://dx.doi.org/10.1155/2017/6468356 |
| spellingShingle | Silvia Biggi Lucia Buccarello Alessandra Sclip Pellegrino Lippiello Noemi Tonna Cristiano Rumio Daniele Di Marino Maria Concetta Miniaci Tiziana Borsello Evidence of Presynaptic Localization and Function of the c-Jun N-Terminal Kinase Neural Plasticity |
| title | Evidence of Presynaptic Localization and Function of the c-Jun N-Terminal Kinase |
| title_full | Evidence of Presynaptic Localization and Function of the c-Jun N-Terminal Kinase |
| title_fullStr | Evidence of Presynaptic Localization and Function of the c-Jun N-Terminal Kinase |
| title_full_unstemmed | Evidence of Presynaptic Localization and Function of the c-Jun N-Terminal Kinase |
| title_short | Evidence of Presynaptic Localization and Function of the c-Jun N-Terminal Kinase |
| title_sort | evidence of presynaptic localization and function of the c jun n terminal kinase |
| url | http://dx.doi.org/10.1155/2017/6468356 |
| work_keys_str_mv | AT silviabiggi evidenceofpresynapticlocalizationandfunctionofthecjunnterminalkinase AT luciabuccarello evidenceofpresynapticlocalizationandfunctionofthecjunnterminalkinase AT alessandrasclip evidenceofpresynapticlocalizationandfunctionofthecjunnterminalkinase AT pellegrinolippiello evidenceofpresynapticlocalizationandfunctionofthecjunnterminalkinase AT noemitonna evidenceofpresynapticlocalizationandfunctionofthecjunnterminalkinase AT cristianorumio evidenceofpresynapticlocalizationandfunctionofthecjunnterminalkinase AT danieledimarino evidenceofpresynapticlocalizationandfunctionofthecjunnterminalkinase AT mariaconcettaminiaci evidenceofpresynapticlocalizationandfunctionofthecjunnterminalkinase AT tizianaborsello evidenceofpresynapticlocalizationandfunctionofthecjunnterminalkinase |