Arginine methylation outside the nucleus: regulation of neuronal synapse development via RNA-binding proteins and kinesin motors

Neurons receive most excitatory synaptic inputs at dendritic spines, which are actin-enriched compartments that undergo dynamic changes during development and memory formation. The development of dendritic spine requires specific RNA-binding proteins, which serve to carry mRNAs along the microtubule from soma to dendrite via the kinesin motor protein, as well as to regulate their local translation near synapses. Deficiency of these RNA-binding proteins may lead to production of immature dendritic spines that are associated with neurodevelopmental disorders. Many RNA-binding proteins present in the dendrite also contain RGG motifs which are hot spots of arginine methylation, indicating the importance of this post-translational modification may extend beyond its conventional function in gene transcription. Here I will describe the regulation of synaptic actin cytoskeleton by PRMT8, an unusual membrane-bound arginine methyltransferase that is localized at neuronal synapses and up-regulated in the hippocampus during dendritic spine development. PRMT8 induces arginine methylation of G3BP1 within the RGG motif and limits immature spine formation via the control of Rac1-PAK signaling, actin dynamics and mRNA translation. I will further describe the methylation of the kinesin motor KIF5B at the carboxyl-terminus, which might regulate binding to specific cargoes. Arginine methylation therefore has a unconventional role in the brain via the control of intracellular transport and cytoskeleton of neurons.