Arc Oligomerization Is Regulated by CaMKII Phosphorylation of the GAG Domain: An Essential Mechanism for Plasticity and Memory Formation.
Mol Cell
; 75(1): 13-25.e5, 2019 07 11.
Article
en En
| MEDLINE
| ID: mdl-31151856
ABSTRACT
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células de Purkinje
/
Potenciación a Largo Plazo
/
Proteínas del Citoesqueleto
/
Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina
/
Memoria
/
Proteínas del Tejido Nervioso
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos