The translation initiating factor eIF4E and arginine methylation underlie G3BP1 function in dendritic spine development of neurons

作者：Dong, Rui; Li, Xuejun; Flores, Angelo D.; Lai, Kwok-On^*

来源：Journal of Biological Chemistry, 2023, 299(8): 105029.

DOI：10.1016/j.jbc.2023.105029

• MESSENGER-RNA TRANSPORT
• STRESS GRANULES
• PROTEIN
• PHOSPHORYLATION
• BINDING
• SYNAPTOGENESIS
• DEMETHYLATION
• METABOLISM
• MORPHOLOGY
• FILOPODIA

Communication between neurons relies on neurotransmission that takes place at synapses. Excitatory synapses are located primarily on dendritic spines that possess diverse morphologies, ranging from elongated filopodia to mushroomshaped spines. Failure in the proper development of dendritic spines has detrimental consequences on neuronal connectivity, but the molecular mechanism that controls the balance of filopodia and mushroom spines is not well understood. G3BP1 is the key RNA-binding protein that assembles the stress granules in non-neuronal cells to adjust protein synthesis upon exogenous stress. Emerging evidence suggests that the biological significance of G3BP1 extends beyond its role in stress response, especially in the nervous system. However, the mechanism underlying the regulation and function of G3BP1 in neurons remains elusive. Here we found that G3BP1 suppresses protein synthesis and binds to the translation initiation factor eIF4E via its NTF2-like domain. Notably, the overproduction of filopodia caused by G3BP1 depletion can be alleviated by blocking the formation of the translation initiation complex. We further found that the interaction of G3BP1 with eIF4E is regulated by arginine methylation. Knockdown of elevated protein synthesis and filopodia production, which is response.