Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral Organoids
Cystatin B (CSTB) is a ubiquitous protein belonging to a superfamily of protease inhibitors. CSTB may play a critical role in brain physiology because its mutations cause progressive myoclonic epilepsy-1A (EPM1A), the most common form of progressive myoclonic epilepsy. However, the molecular mechani...
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doaj-e94d7d022b3e4ede8da5f59282e584d32020-11-25T02:03:08ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992019-08-011210.3389/fnmol.2019.00195471697Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral OrganoidsEduardo Penna0Angela Cerciello1Angela Chambery2Rosita Russo3Filippo M. Cernilogar4Emilia Maria Pedone5Carla Perrone-Capano6Carla Perrone-Capano7Silvia Cappello8Rossella Di Giaimo9Rossella Di Giaimo10Marianna Crispino11Department of Biology, University of Naples Federico II, Naples, ItalyDepartment of Biology, University of Naples Federico II, Naples, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, Caserta, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, Caserta, ItalyDivision of Molecular Biology, Biomedical Center, Faculty of Medicine, LMU, Munich, GermanyInstitute of Biostructures and Bioimaging, National Research Council (CNR), Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, Naples, ItalyInstitute of Genetics and Biophysics “Adriano Buzzati Traverso”, National Research Council (CNR), Naples, ItalyDepartment of Developmental Neurobiology, Max Planck Institute of Psychiatry, Munich, GermanyDepartment of Biology, University of Naples Federico II, Naples, ItalyDepartment of Developmental Neurobiology, Max Planck Institute of Psychiatry, Munich, GermanyDepartment of Biology, University of Naples Federico II, Naples, ItalyCystatin B (CSTB) is a ubiquitous protein belonging to a superfamily of protease inhibitors. CSTB may play a critical role in brain physiology because its mutations cause progressive myoclonic epilepsy-1A (EPM1A), the most common form of progressive myoclonic epilepsy. However, the molecular mechanisms underlying the role of CSTB in the central nervous system (CNS) are largely unknown. To investigate the possible involvement of CSTB in the synaptic plasticity, we analyzed its expression in synaptosomes as a model system in studying the physiology of the synaptic regions of the CNS. We found that CSTB is not only present in the synaptosomes isolated from rat and mouse brain cortex, but also secreted into the medium in a depolarization-controlled manner. In addition, using biorthogonal noncanonical amino acid tagging (BONCAT) procedure, we demonstrated, for the first time, that CSTB is locally synthesized in the synaptosomes. The synaptic localization of CSTB was confirmed in a human 3D model of cortical development, namely cerebral organoids. Altogether, these results suggest that CSTB may play a role in the brain plasticity and open a new perspective in studying the involvement of CSTB deregulation in neurodegenerative and neuropsychiatric diseases.https://www.frontiersin.org/article/10.3389/fnmol.2019.00195/fullCSTBsynaptosomesEPM1Acerebral organoidssynaptic plasticitylocal protein synthesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eduardo Penna Angela Cerciello Angela Chambery Rosita Russo Filippo M. Cernilogar Emilia Maria Pedone Carla Perrone-Capano Carla Perrone-Capano Silvia Cappello Rossella Di Giaimo Rossella Di Giaimo Marianna Crispino |
spellingShingle |
Eduardo Penna Angela Cerciello Angela Chambery Rosita Russo Filippo M. Cernilogar Emilia Maria Pedone Carla Perrone-Capano Carla Perrone-Capano Silvia Cappello Rossella Di Giaimo Rossella Di Giaimo Marianna Crispino Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral Organoids Frontiers in Molecular Neuroscience CSTB synaptosomes EPM1A cerebral organoids synaptic plasticity local protein synthesis |
author_facet |
Eduardo Penna Angela Cerciello Angela Chambery Rosita Russo Filippo M. Cernilogar Emilia Maria Pedone Carla Perrone-Capano Carla Perrone-Capano Silvia Cappello Rossella Di Giaimo Rossella Di Giaimo Marianna Crispino |
author_sort |
Eduardo Penna |
title |
Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral Organoids |
title_short |
Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral Organoids |
title_full |
Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral Organoids |
title_fullStr |
Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral Organoids |
title_full_unstemmed |
Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral Organoids |
title_sort |
cystatin b involvement in synapse physiology of rodent brains and human cerebral organoids |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Neuroscience |
issn |
1662-5099 |
publishDate |
2019-08-01 |
description |
Cystatin B (CSTB) is a ubiquitous protein belonging to a superfamily of protease inhibitors. CSTB may play a critical role in brain physiology because its mutations cause progressive myoclonic epilepsy-1A (EPM1A), the most common form of progressive myoclonic epilepsy. However, the molecular mechanisms underlying the role of CSTB in the central nervous system (CNS) are largely unknown. To investigate the possible involvement of CSTB in the synaptic plasticity, we analyzed its expression in synaptosomes as a model system in studying the physiology of the synaptic regions of the CNS. We found that CSTB is not only present in the synaptosomes isolated from rat and mouse brain cortex, but also secreted into the medium in a depolarization-controlled manner. In addition, using biorthogonal noncanonical amino acid tagging (BONCAT) procedure, we demonstrated, for the first time, that CSTB is locally synthesized in the synaptosomes. The synaptic localization of CSTB was confirmed in a human 3D model of cortical development, namely cerebral organoids. Altogether, these results suggest that CSTB may play a role in the brain plasticity and open a new perspective in studying the involvement of CSTB deregulation in neurodegenerative and neuropsychiatric diseases. |
topic |
CSTB synaptosomes EPM1A cerebral organoids synaptic plasticity local protein synthesis |
url |
https://www.frontiersin.org/article/10.3389/fnmol.2019.00195/full |
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