The Protein Arginine Methyltransferase PRMT8 and Substrate G3BP1 Control Rac1-PAK1 Signaling and Actin Cytoskeleton for Dendritic Spine Maturation

• Published in: Cell reports (Cambridge) 2020-06, Vol.31 (10), p.107744-107744, Article 107744
• Main Authors: Lo, Louisa Hoi-Ying, Dong, Rui, Lyu, Quanwei, Lai, Kwok-On
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - metabolism; actin dynamics; Animals; Arginine - metabolism; arginine methylation; cytoskeleton; dendritic spine; Dendritic Spines - metabolism; DNA Helicases - metabolism; Female; GTPase; HEK293 Cells; Humans; local translation; Male; Membrane Proteins - metabolism; Methylation; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Poly-ADP-Ribose Binding Proteins - metabolism; post-translational modification; Protein Processing, Post-Translational; Protein-Arginine N-Methyltransferases - metabolism; Rats; Rats, Sprague-Dawley; RNA Helicases - metabolism; RNA Recognition Motif Proteins - metabolism; RNA-binding protein; Signal Transduction; synapse; Synapses - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.107744

Excitatory synapses of neurons are located on dendritic spines. Spine maturation is essential for the stability of synapses and memory consolidation, and overproduction of the immature filopodia is associated with brain disorders. The structure and function of synapses can be modulated by protein post-translational modification (PTM). Arginine methylation is a major PTM that regulates chromatin structure, transcription, and splicing within the nucleus. Here we find that the protein arginine methyltransferase PRMT8 is present at neuronal synapses and its expression is upregulated in the hippocampus when dendritic spine maturation occurs. Depletion of PRMT8 leads to overabundance of filopodia and mis-localization of excitatory synapses. Mechanistically, PRMT8 promotes dendritic spine morphology through methylation of the dendritic RNA-binding protein G3BP1 and suppression of the Rac1-PAK1 signaling pathway to control synaptic actin dynamics. Our findings unravel arginine methylation as a crucial regulatory mechanism for actin cytoskeleton during synapse development. [Display omitted] •PRMT8 is upregulated in hippocampus during dendritic spine maturation•Depletion of PRMT8 generates more filopodia•Lack of PRMT8 increases cofilin phosphorylation and slows actin turnover•Spine maturation depends on arginine methylation of the PRMT8 substrate G3BP1 Lo et al. demonstrate that PRMT8 is localized at neuronal synapses and methylates the dendritic RNA-binding protein G3BP1. This promotes synapse maturation by regulating Rac1 and synaptic actin dynamics. Therefore, arginine methylation, a well-known protein modification in the nucleus, also acts in dendrites to control neuronal development.