PRMT3 is essential for dendritic spine maturation in rat hippocampal neurons.
Protein arginine N-methyltransferase 3 (PRMT3) is a cytoplasmic enzyme that utilizes S-adenosyl-L-methionine (AdoMet) to methylate specific proteins, most of which contain GAR (glycine-arginine rich) motifs. PRMT3 has been shown to play a role in the proper maturation of the 80S ribosome by binding to and catalyzing the methylation of rpS2, a component of the 40S ribosomal subunit. However, the other roles of PRMT3 are fairly unclear, particularly in the brain, which is abundant in methylated proteins. In this study, we perturbed PRMT3 expression in cultured rat hippocampal neurons by transiently introducing siRNA oligonucleotides that were designed to hybridize with PRMT3 mRNA and then we examined the morphological and functional effects of neuronal PRMT3 depletion. PRMT3-defective neurons showed deformed spines without any change in spine number; less BDNF-induced protein translation of alphaCaMKII; and diminished rpS2 protein stability. Furthermore, overexpression of a methylation-resistant rpS2, whose methylated arginine residues were deleted, produced phenotypes that were similar to those associated with PRMT3 downregulation. These findings demonstrated that PRMT3 possibly plays a pivotal role in neuronal translation by interaction with rpS2 and that it contributes to activity-dependent changes in the dendritic spines.
Miyata
Shingo
S
Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. smiyata@anat2.med.osaka-u.ac.jp
Mori
Yasutake
Y
Tohyama
Masaya
M
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D017931:DNA Primers; D049229:Dendritic Spines / Q000201:enzymology / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D006624:Hippocampus / Q000254:growth & development*; D006801:Humans; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009474:Neurons / Q000502:physiology*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012269:Ribosomal Proteins / Q000235:genetics; D013574:Synaptosomes / Q000201:enzymology
D017931:DNA Primers; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins; C413164:PRMT3 protein, human; D011484:Protein-Arginine N-Methyltransferases