Arc Oligomerization Is Regulated by CaMKII Phosphorylation of the GAG Domain: An Essential Mechanism for Plasticity and Memory Formation.
Amino Acid Sequence
Amygdala
/ cytology
Animals
Binding Sites
Calcium-Calmodulin-Dependent Protein Kinase Type 2
/ chemistry
Cytoskeletal Proteins
/ chemistry
Gene Knock-In Techniques
HEK293 Cells
Hippocampus
/ cytology
Humans
Long-Term Potentiation
/ physiology
Memory
/ physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Models, Molecular
Nerve Tissue Proteins
/ chemistry
Phosphorylation
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Protein Multimerization
Purkinje Cells
/ cytology
Sequence Alignment
Sequence Homology, Amino Acid
Synapses
/ physiology
Synaptic Transmission
Arc
CAMKII
capsid
evolution
learning and memory
phosphorylation
polymerization
synapse plasticity
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
11 07 2019
11 07 2019
Historique:
received:
28
11
2018
revised:
27
03
2019
accepted:
01
05
2019
pubmed:
4
6
2019
medline:
14
1
2020
entrez:
2
6
2019
Statut:
ppublish
Résumé
Arc is a synaptic protein essential for memory consolidation. Recent studies indicate that Arc originates in evolution from a Ty3-Gypsy retrotransposon GAG domain. The N-lobe of Arc GAG domain acquired a hydrophobic binding pocket in higher vertebrates that is essential for Arc's canonical function to weaken excitatory synapses. Here, we report that Arc GAG also acquired phosphorylation sites that can acutely regulate its synaptic function. CaMKII phosphorylates the N-lobe of the Arc GAG domain and disrupts an interaction surface essential for high-order oligomerization. In Purkinje neurons, CaMKII phosphorylation acutely reverses Arc's synaptic action. Mutant Arc that cannot be phosphorylated by CaMKII enhances metabotropic receptor-dependent depression in the hippocampus but does not alter baseline synaptic transmission or long-term potentiation. Behavioral studies indicate that hippocampus- and amygdala-dependent learning requires Arc GAG domain phosphorylation. These studies provide an atomic model for dynamic and local control of Arc function underlying synaptic plasticity and memory.
Identifiants
pubmed: 31151856
pii: S1097-2765(19)30357-0
doi: 10.1016/j.molcel.2019.05.004
pmc: PMC6625847
mid: NIHMS1528764
pii:
doi:
Substances chimiques
Cytoskeletal Proteins
0
Nerve Tissue Proteins
0
activity regulated cytoskeletal-associated protein
0
Calcium-Calmodulin-Dependent Protein Kinase Type 2
EC 2.7.11.17
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13-25.e5Subventions
Organisme : NIA NIH HHS
ID : P30 AG066507
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH100024
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH053608
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097966
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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