DNA Methylation-Mediated Modulation of Endocytosis as Potential Mechanism for Synaptic Function Regulation in Murine Inhibitory Cortical Interneurons.


Journal

Cerebral cortex (New York, N.Y. : 1991)
ISSN: 1460-2199
Titre abrégé: Cereb Cortex
Pays: United States
ID NLM: 9110718

Informations de publication

Date de publication:
01 06 2020
Historique:
received: 05 09 2019
revised: 14 12 2019
accepted: 10 01 2020
pubmed: 10 3 2020
medline: 17 12 2021
entrez: 10 3 2020
Statut: ppublish

Résumé

The balance of excitation and inhibition is essential for cortical information processing, relying on the tight orchestration of the underlying subcellular processes. Dynamic transcriptional control by DNA methylation, catalyzed by DNA methyltransferases (DNMTs), and DNA demethylation, achieved by ten-eleven translocation (TET)-dependent mechanisms, is proposed to regulate synaptic function in the adult brain with implications for learning and memory. However, focus so far is laid on excitatory neurons. Given the crucial role of inhibitory cortical interneurons in cortical information processing and in disease, deciphering the cellular and molecular mechanisms of GABAergic transmission is fundamental. The emerging relevance of DNMT and TET-mediated functions for synaptic regulation irrevocably raises the question for the targeted subcellular processes and mechanisms. In this study, we analyzed the role dynamic DNA methylation has in regulating cortical interneuron function. We found that DNMT1 and TET1/TET3 contrarily modulate clathrin-mediated endocytosis. Moreover, we provide evidence that DNMT1 influences synaptic vesicle replenishment and GABAergic transmission, presumably through the DNA methylation-dependent transcriptional control over endocytosis-related genes. The relevance of our findings is supported by human brain sample analysis, pointing to a potential implication of DNA methylation-dependent endocytosis regulation in the pathophysiology of temporal lobe epilepsy, a disease characterized by disturbed synaptic transmission.

Identifiants

pubmed: 32147726
pii: 5799017
doi: 10.1093/cercor/bhaa009
pmc: PMC7264686
doi:

Substances chimiques

Clathrin 0
Cytoskeletal Proteins 0
DNA-Binding Proteins 0
Intracellular Signaling Peptides and Proteins 0
Proto-Oncogene Proteins 0
TET1 protein, mouse 0
WIPF1 protein, human 0
Dioxygenases EC 1.13.11.-
Tet3 protein, mouse EC 1.13.11.-
DNA (Cytosine-5-)-Methyltransferase 1 EC 2.1.1.37
Dnmt1 protein, mouse EC 2.1.1.37

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3921-3937

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press.

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Auteurs

Daniel Pensold (D)

Institute of Human Genetics, University Hospital Jena, 07743 Jena, Germany.
Division of Functional Epigenetics, Institute of Zoology (Biology 2), RWTH Aachen University, 52074 Aachen, Germany.

Julia Reichard (J)

Institute of Human Genetics, University Hospital Jena, 07743 Jena, Germany.
Division of Functional Epigenetics, Institute of Zoology (Biology 2), RWTH Aachen University, 52074 Aachen, Germany.
Research Training Group 2416 Multi Senses-Multi Scales, RWTH Aachen University, 52074 Aachen, Germany.

Karen M J Van Loo (KMJ)

Department of Neuropathology, Section for Translational Epilepsy Research, University of Bonn Medical Center, 53105 Bonn, Germany.

Natalja Ciganok (N)

Division of Systems Neurophysiology, Institute of Zoology (Biology 2), RWTH Aachen University, 52074 Aachen, Germany.

Anne Hahn (A)

Institute of Human Genetics, University Hospital Jena, 07743 Jena, Germany.

Cathrin Bayer (C)

Institute of Human Genetics, University Hospital Jena, 07743 Jena, Germany.
Division of Functional Epigenetics, Institute of Zoology (Biology 2), RWTH Aachen University, 52074 Aachen, Germany.

Lutz Liebmann (L)

Institute of Human Genetics, University Hospital Jena, 07743 Jena, Germany.

Jonas Groß (J)

Institute of Human Genetics, University Hospital Jena, 07743 Jena, Germany.

Jessica Tittelmeier (J)

Institute of Human Genetics, University Hospital Jena, 07743 Jena, Germany.

Thomas Lingner (T)

Department of Developmental Biochemistry, Transcriptome and Genome Analysis Laboratory (TAL), University of Goettingen, 37077 Goettingen, Germany.

Gabriela Salinas-Riester (G)

Department of Developmental Biochemistry, Transcriptome and Genome Analysis Laboratory (TAL), University of Goettingen, 37077 Goettingen, Germany.

Judit Symmank (J)

Institute of Human Genetics, University Hospital Jena, 07743 Jena, Germany.

Claas Halfmann (C)

Division of Systems Neurophysiology, Institute of Zoology (Biology 2), RWTH Aachen University, 52074 Aachen, Germany.

Lourdes González-Bermúdez (L)

Institute of Human Genetics, University Hospital Jena, 07743 Jena, Germany.

Anja Urbach (A)

Clinic for Neurology, University Hospital Jena, 07743 Jena, Germany.

Julia Gehrmann (J)

Institute for Computational Genomics, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany.

Ivan Costa (I)

Institute for Computational Genomics, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany.

Tomas Pieler (T)

Department of Developmental Biochemistry, Centre for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), University of Goettingen, 37077 Goettingen, Germany.

Christian A Hübner (CA)

Institute of Human Genetics, University Hospital Jena, 07743 Jena, Germany.

Hartmut Vatter (H)

Clinic for Neurosurgery, University of Bonn Medical Center, 53105 Bonn, Germany.

Björn Kampa (B)

Division of Systems Neurophysiology, Institute of Zoology (Biology 2), RWTH Aachen University, 52074 Aachen, Germany.
JARA BRAIN, Institute for Neuroscience and Medicine, Forschungszentrum Jülich, 52425, Germany.

Albert J Becker (AJ)

Department of Neuropathology, Section for Translational Epilepsy Research, University of Bonn Medical Center, 53105 Bonn, Germany.

Geraldine Zimmer-Bensch (G)

Institute of Human Genetics, University Hospital Jena, 07743 Jena, Germany.
Division of Functional Epigenetics, Institute of Zoology (Biology 2), RWTH Aachen University, 52074 Aachen, Germany.
Research Training Group 2416 Multi Senses-Multi Scales, RWTH Aachen University, 52074 Aachen, Germany.

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