Synaptic homeostasis is regulated by the kinesin motor protein Khc-73 in Drosophila melanogaster. Edward H. Liao, Kazuya Tsurudome, Wassim El Mounzer, Frances Wang, Fatima Elazzouzi, Pejmun Haghighi. Dept Physiology, McGill University, Montreal, QC, Canada.

   Accumulating evidence suggests that homeostatic mechanisms participate in stabilizing function in neural circuits; however, we know little about the molecular mechanisms that control synaptic homeostasis. Previously, we have demonstrated that overexpression of a microRNA cluster that targets a member of the kinesin 3 family of motor proteins, Khc-73, suppresses the expression of a compensatory homeostatic synaptic response at the Drosophila larval neuromuscular junction (NMJ). Here we describe the characterization of a loss-of-function Khc-73 mutant. NMJ baseline electrophysiological properties as well as the number of synaptic boutons at NMJs in Khc-73 mutant larvae appear indistinguishable from wild type. However, consistent with our previous observations, the normal retrograde, homeostatic response at the NMJ is severely affected in these mutants. As normal synaptic compensation requires an enhancement of neurotransmitter release, we examined in more detail the accumulation and structure of active zones both at the level of light microscopy and electron microscopy. Our findings suggest that Khc-73 is required for the normal appearance of active zone protein Bruch pilot at the NMJ as well as the number of electron dense T-bars at active zones. Little experimental data is available that links the lack of normal homeostatic control to the overall behavioural outcome. We therefore tested the consequence of loss of Khc-73 on lifespan and locomotion in adult flies. While Khc-73 homozygous adults are viable, we observed a significant reduction in their lifespan. In addition, Khc-73 mutants showed reduced ability to climb and fly. We are currently using genetic approaches to identify the circuitry that is most affected as a result of loss of Khc-73.