View Program - 63rd Annual Drosophila Research Conference

Neurons are morphologically elaborate and long-living cells. Both features put special demands on membrane trafficking. Rab GTPases are regulators of membrane trafficking and the Drosophila genome encodes 26 rab genes. All rabs are expressed in the nervous system and 13 of the 26 rabs exhibit nervous system-enriched expression patterns. To facilitate systematic functional analyses of neuron-specific membrane trafficking, we have generated a complete rab null mutant collection. Remarkably, the complete loss of any of the 13 nervous system-enriched Rabs did not cause obvious defects concerning fly survival, fertility, or morphology under laboratory conditions. However, under challenging conditions including continuous neuronal stimulation or temperature variation all rab mutants revealed specific sensitivities affecting development, function, or maintenance of the nervous system. Our observations suggest that the majority of Rabs serve modulatory functions that ensure robustness of development or function to challenging environmental conditions.
We followed up on our initial systematic characterization with a more detailed analysis of four neuronal or neuron-enriched rabs: rab26, rab19, rabX1 and rabX4. Rab26 has previously been proposed to link synaptic vesicle recycling and autophagy. However, our characterization of the rab26 mutant revealed no autophagosomal or synaptic vesicle defects in flies. Instead, we found an activity-dependent role of Rab26 in receptor trafficking at cholinergic synapses. Our analyses of rab26, rab19, rabX1 and rabX4 revealed synthetic lethality for double mutants of rabX1 with each of the other three, but no other double mutant combination. We will present an update on our characterization of the functional contributions of each of these rabs.

Systematic functional analysis of Rab GTPases in neuronal development and maintenance