Loss of 4E-BP converts cerebellar long-term depression to long-term potentiation.

Adaptor Proteins, Signal Transducing / genetics Animals Cell Cycle Proteins / genetics Cerebellum / physiology Long-Term Potentiation / physiology Long-Term Synaptic Depression / physiology Mammals Mice Neuronal Plasticity / physiology Phosphoric Monoester Hydrolases Purkinje Cells / physiology Synapses / physiology
4E-BP CP: Neuroscience LTD PP2A Purkinje cells autism cerebellum mTOR phosphatase kinase balance synaptic plasticity translation

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
07 06 2022
Historique:
received: 16 03 2021
revised: 31 10 2021
accepted: 12 05 2022
entrez: 8 6 2022
pubmed: 9 6 2022
medline: 11 6 2022
Statut: ppublish

Résumé

Genetic perturbances in translational regulation result in defects in cerebellar motor learning; however, little is known about the role of translational mechanisms in the regulation of cerebellar plasticity. We show that genetic removal of 4E-BP, a translational suppressor and target of mammalian target of rapamycin complex 1, results in a striking change in cerebellar synaptic plasticity. We find that cerebellar long-term depression (LTD) at parallel fiber-Purkinje cell synapses is converted to long-term potentiation in 4E-BP knockout mice. Biochemical and pharmacological experiments suggest that increased phosphatase activity largely accounts for the defects in LTD. Our results point to a model in which translational regulation through the action of 4E-BP plays a critical role in establishing the appropriate kinase/phosphatase balance required for normal synaptic plasticity in the cerebellum.

Identifiants

DOI: 10.1016/j.celrep.2022.110911 PMID: 35675781
pubmed: 35675781
pii: S2211-1247(22)00688-X
doi: 10.1016/j.celrep.2022.110911
pii:
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
Cell Cycle Proteins 0
Eif4ebp1 protein, mouse 0
Phosphoric Monoester Hydrolases EC 3.1.3.2

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

110911

Subventions

Organisme : CIHR
Pays : Canada

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors have no financial interests or conflicts of interest.

Auteurs

Natasha Saviuk (N)

Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada; Department of Physiology, McGill University, Montréal, QC, Canada.

Yumaine Chong (Y)

Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada; Department of Physiology, McGill University, Montréal, QC, Canada.

Peng Wang (P)

Biochemistry, McGill University, Montréal, QC, Canada.

Sara Bermudez (S)

Biochemistry, McGill University, Montréal, QC, Canada.

Zhe Zhao (Z)

Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada.

Arjun A Bhaskaran (AA)

Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada; Pharmacology and Therapeutics, McGill University, Montréal, QC, Canada.

Derek Bowie (D)

Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada; Pharmacology and Therapeutics, McGill University, Montréal, QC, Canada.

Nahum Sonenberg (N)

Biochemistry, McGill University, Montréal, QC, Canada.

Ellis Cooper (E)

Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada; Department of Physiology, McGill University, Montréal, QC, Canada. Electronic address: ellis.cooper@mcgill.ca.

A Pejmun Haghighi (AP)

Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada; Department of Physiology, McGill University, Montréal, QC, Canada; Buck Institute for Research on Aging, Novato, CA, USA. Electronic address: phaghighi@buckinstitute.org.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Loss of 4E-BP converts cerebellar long-term...
questionsmedicales.fr › Eucaryotes › Animaux › Loss of 4E-BP converts cerebellar long-term...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cycle cellulaire › Loss of 4E-BP converts cerebellar long-term...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Tronc cérébral › Rhombencéphale › Métencéphale › Cervelet › Loss of 4E-BP converts cerebellar long-term...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Plasticité neuronale › Potentialisation à long terme › Loss of 4E-BP converts cerebellar long-term...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Plasticité neuronale › Dépression synaptique à long terme › Loss of 4E-BP converts cerebellar long-term...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Loss of 4E-BP converts cerebellar long-term...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Loss of 4E-BP converts cerebellar long-term...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Plasticité neuronale › Loss of 4E-BP converts cerebellar long-term...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Phosphoric monoester hydrolases › Loss of 4E-BP converts cerebellar long-term...
questionsmedicales.fr › Cellules › Neurones › Cellules de Purkinje › Loss of 4E-BP converts cerebellar long-term...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › Structures de la membrane cellulaire › Jonctions intercellulaires › Synapses › Loss of 4E-BP converts cerebellar long-term...