Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function.

Nervous system function rests on the formation of functional synapses between neurons. We have identified TRMT9B as a new regulator of synapse formation and function in Drosophila. TRMT9B has been studied for its role as a tumor suppressor and is one of two metazoan homologs of yeast tRNA methyltransferase 9 (Trm9), which methylates tRNA wobble uridines. Whereas Trm9 homolog ALKBH8 is ubiquitously expressed, TRMT9B is enriched in the nervous system. However, in the absence of animal models, TRMT9B's role in the nervous system has remained unstudied. Here, we generate null alleles of TRMT9B and find it acts postsynaptically to regulate synaptogenesis and promote neurotransmission. Through liquid chromatography-mass spectrometry, we find that ALKBH8 catalyzes canonical tRNA wobble uridine methylation, raising the question of whether TRMT9B is a methyltransferase. Structural modeling studies suggest TRMT9B retains methyltransferase function and, in vivo, disruption of key methyltransferase residues blocks TRMT9B's ability to rescue synaptic overgrowth, but not neurotransmitter release. These findings reveal distinct roles for TRMT9B in the nervous system and highlight the significance of tRNA methyltransferase family diversification in metazoans.

Gallium nanoparticles as novel inhibitors of Aß40 aggregation.

Alzheimer's disease (AD) has been consistently related to the formation of senile amyloid plaques mainly composed of amyloid ß (Aß) peptides. The toxicity of Aß aggregates has been indicated to be responsible for AD pathology. One scenario to decrease Aß toxicity is the development of effective inhibitors against Aß amyloid formation. In this study, we investigate the effect of gallium nitride nanoparticles (GaN NPs) as inhibitors of Aß40 amyloid formation using a combination of biophysical approaches. Our results show that the lag phase of Aß40 aggregation kinetics is significantly retarded by GaN NPs in a concentration dependent manner, implying the activity of GaN NPs in interfering with the formation of the crucial nucleus during Aß aggregation. Our results also show that GaN NPs can reduce the amyloid fibril elongation rate in the course of the aggregation kinetics. It is speculated that the high polarization characteristics of GaN NPs may provoke a strong interaction between the particles and Aß40 peptide and in this way decrease self-association of the peptide monomers to form amyloids.