The Role of Protein Arginine Methylation as Post-Translational Modification on Actin Cytoskeletal Components in Neuronal Structure and Function

Abstract

The brain encompasses a complex network of neurons with exceptionally elaborated morphologies of their axonal (signal-sending) and dendritic (signal-receiving) parts. De novo actin filament formation is one of the major driving and steering forces for the development and plasticity of the neuronal arbor. Actin filament assembly and dynamics thus require tight temporal and spatial control. Such control is particularly effective at the level of regulating actin nucleation-promoting factors, as these are key components for filament formation. Arginine methylation represents an important post-translational regulatory mechanism that had previously been mainly associated with controlling nuclear processes. We will review and discuss emerging evidence from inhibitor studies and loss-of-function models for protein arginine methyltransferases (PRMTs), both in cells and whole organisms, that unveil that protein arginine methylation mediated by PRMTs represents an important regulatory mechanism in neuritic arbor formation, as well as in dendritic spine induction, maturation and plasticity. Recent results furthermore demonstrated that arginine methylation regulates actin cytosolic cytoskeletal components not only as indirect targets through additional signaling cascades, but can also directly control an actin nucleation-promoting factor shaping neuronal cells—a key process for the formation of neuronal networks in vertebrate brains.

Cognitive impairments in a Down syndrome model with abnormal hippocampal and prefrontal dynamics and cytoarchitecture

“… 83 , 84 More importantly, S100B levels are elevated in the brain of people with DS 85 , 86 and in the HPC of the Dp(10)2Yey mouse model (unpublished data). PRMT2 has a role in neuritic arbor formation and dendritic spine induction, maturation, and plasticity, 87 and human PRMT orthologs play a part in cell proliferation via mTOR signaling. 88 Similarly, in humans ADARB1 increases cell proliferation and migration by regulating mTOR signaling.…”

Associations of Methylenetetrahydrofolate reductase (MTHFR) polymorphism with Hepatocellular carcinoma In Egyptian population.

“…Methylation is an essential biochemical mechanism that is central to the transmission of life, and crucially responsible for regulating gametogenesis and continued embryo development [33]. Brain development and its maturation also depend on correct lipid methylation, and continued neuronal function depends on biogenic amines that require methylation for their synthesis [34].…”

Activity and Function of the PRMT8 Protein Arginine Methyltransferase in Neurons

“…Most PRMTs contain one catalytic Rossman fold domain, but dimerization through the β-barrel is required to compose the active enzyme. While the catalytic core domain of all PRMTs is structurally conserved, the N-terminal non-catalytic domain is very diverse among family members [5]. For example, PRMT3 contains a zinc finger motif which is required for its interaction with the ribosomal protein rpS2 to recognize RNA-associated substrates [6,7]; in contrast, PRMT5 contains a TIM barrel which is responsible for its interaction with the WD40 repeat protein MEP50 [8,9].…”