Cdh1-APC Regulates Protein Synthesis and Stress Granules in Neurons through an FMRP-Dependent Mechanism.
iScience
; 23(5): 101132, 2020 May 22.
Article
em En
| MEDLINE
| ID: mdl-32434143
ABSTRACT
Maintaining a balance between protein degradation and protein synthesis is necessary for neurodevelopment. Although the E3 ubiquitin ligase anaphase promoting complex and its regulatory subunit Cdh1 (Cdh1-APC) has been shown to regulate learning and memory, the underlying mechanisms are unclear. Here, we have identified a role of Cdh1-APC as a regulator of protein synthesis in neurons. Proteomic profiling revealed that Cdh1-APC interacts with known regulators of translation, including stress granule proteins. Inhibition of Cdh1-APC activity caused an increase in stress granule formation that is dependent on fragile X mental retardation protein (FMRP). We propose a model in which Cdh1-APC targets stress granule proteins, such as FMRP, and inhibits the formation of stress granules, leading to protein synthesis. Elucidation of a role for Cdh1-APC in regulation of stress granules and protein synthesis in neurons has implications for how Cdh1-APC can regulate protein-synthesis-dependent synaptic plasticity underlying learning and memory.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article