831B Poster - 13. Neural development and physiology
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Ambar Delgado ¹; Kimberly Rose Madhwani ²; Caley Hogan ³; Jennifer Dumouchel ⁴; Kate O'Connor-Giles ^1,5

Affiliations:
1) Department of Neuroscience, Brown University, Providence, RI; 2) Neuroscience Graduate Training Program, Brown University, Providence, RI; 3) Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI; 4) Therapeutic Sciences Graduate Training Program, Brown University, Providence, RI; 5) Carney Institute for Brain Science, Brown University, Providence, RI

Keywords:
f. neuromuscular junction; e. synaptic function and organization

The nervous system is highly dependent on the dynamic regulation of translation. Posttranscriptional modification of RNAs is emerging as a key regulator of protein synthesis. tRNAs are extensively post-transcriptionally modified to regulate their structure, stability, decoding speed, and accuracy. Through a genetic screen in Drosophila to identify new, conserved synaptic genes, we discovered that tRNA methyltransferase family member TRMT9B, also known as fid, negatively regulates synaptic growth. Here, we investigated TRMT9B’s role in regulating neurotransmission under basal conditions and during homeostatic plasticity, and in locomotor behavior. Current clamp electrophysiology at the neuromuscular junction (NMJ) shows a significant decrease in neurotransmitter release in TRMT9B mutants. Considering the presence of ectopic synapses in TRMT9B mutants, this suggests diminished function of individual synapses at the NMJ and a role for TRMT9B in establishing precise synaptic communication.

Synapses modulate their strength during plasticity and to homeostatically maintain function at physiological levels in response to perturbation. At the Drosophila NMJ, disruption of postsynaptic glutamate receptors triggers a compensatory increase in presynaptic neurotransmitter release that precisely offsets the deficit to maintain optimal synaptic communication. Chronic presynaptic homeostatic potentiation (PHP) depends on the dynamic regulation of gene expression, so we investigated the role of TRMT9B in chronic PHP. Interestingly, we found that loss of glutamate receptor IIA resulted in lethality in the absence of TRMT9B. While this lethality precludes electrophysiological analysis, it suggests that long-term homeostatic compensation of neurotransmission may require TRMT9B. Finally, we investigated TRMT9B’s role in locomotion through larval crawling and climbing assays, and observed significant impairment at both developmental stages. Overall, our findings indicate critical roles for TRMT9B in motor function.