Receptor methylation controls behavior

By: James V. Kohl | Published on: November 15, 2015

The protein arginine methyltransferase PRMT5 promotes D2-like dopamine receptor signaling

Excerpt 1)

The addition of a methyl group to an arginine residue can remove a hydrogen bond donor and decrease the electrostatic surface potential at the residue, resulting in a change in size and hydrophobicity that can affect its interaction with binding partners (21).

Excerpt 2)

Together, these results led us to propose that arginine methylation promotes D2-like dopamine receptor signaling and that this mechanism of receptor regulation is conserved between nematodes and humans. Moreover, our finding that several hundred mammalian GPCRs contain predicted methylation sites within their cytoplasmic domains (Fig. 1A and tables S1 and S2) suggests that methylation may broadly regulate GPCR signaling in a previously unappreciated manner.

My comment: This article links RNA-directed DNA methylation to G protein-coupled receptors via biophysically constrained nutrient-dependent pheromone-controlled protein folding chemistry in species from nematodes to humans. It was reported as:

Receptor methylation controls behavior

D2 dopamine receptors are targeted by antipsychotic agents to regulate behavior. Likhite et al. found putative arginine methylation motifs in some human G protein–coupled receptors (GPCRs), including the D2 dopamine receptor, and in homologs in the worm Caenorhabditis elegans. Methylation of the D2 dopamine receptor by the arginine methyltransferase PRMT5 enhanced D2 receptor signaling in cultured cells. C. elegans lacking prmt-5 had behavioral problems similar to those in worms deficient in the D2-like receptor DOP-3. Thus, methylation of GPCRs may be important for clinically relevant targets such as the D2 receptor.

My comment: The claim that Receptor methylation controls behavior can be placed into the context of MicroRNA-encoded behavior in Drosophila, and all other living genera. For example, Feedback loops link odor and pheromone signaling with reproduction.

Indications that GnRH peptide plays an important role in the control of sexual behaviors suggest that pheromone effects on these behaviors might also involve GnRH neurons. (p 683)

My comment: The nutrient-dependent microRNA/messenger RNA balance links energy-dependent base pair changes to RNA-mediated gene duplication and fixation of RNA-mediated amino acid substitutions that differentiate all cell types of all individuals of all living genera in the context of the physiology of reproduction. Even when the physiology of reproduction does not involve neurons, it involves the conserved molecular mechanisms of nutrient-dependent pheromone-controlled reproduction in species from microbes to humans.
See for details: From Fertilization to Adult Sexual Behavior

Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.

My comment: The alternative splicing of otherwise identical genes links everything known about physics, chemistry, and biology via the conserved molecular mechanisms of biophysically constrained nutrient-dependent RNA-mediated protein folding to protection against virus-driven genomic entropy, which is ensured by supercoiled DNA.

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