Neurotransmitter levels and synaptic strength at the Drosophila larval neuromuscular junction are not altered by mutation in the sluggish-A gene, which encodes proline oxidase and affects adult locomotion

The sluggish-A (slgA) gene of Drosophila melanogaster has been shown to enc ode for the enzyme proline oxidase, a mitochondrial enzyme which catalyzes the first step in the conversion of L-proline to L-glutamate. The slgA tran script is expressed in both lan and adult Drosophila melanogaster. Mutation s in this gene lead to reduced proline oxidase activity and an elevation of free proline levels. Adult mutant flies show a striking reduction of motor activity. Since proline oxidase may contribute to the supply of the neurot ransmitter glutamate in the nervous system, a reduction in proline oxidase activity could reduce neural glutamate pools and affect synaptic transmissi on in neurons utilizing glutamate as a transmitter, including peripheral mo tor neurons. We tested the hypothesis that glutamate, and synaptic transmis sion mediated by glutamate, are reduced at synapses of glutamatergic motor neurons in slgA mutants. Levels of glutamate and proline in different cell compartments, and functional properties of synaptic transmission were compa red in slgA and control specimens. Proline is elevated in muscle cells of s lgA mutants, indicating that the slgA gene regulates tissue proline levels. In nerve terminal varicosities, proline levels were low in both mutants an d controls. Glutamate levels in nerve terminal varicosities of slgA mutants and controls were similar. In addition, we found that glutamatergic synapt ic transmission at individual nerve endings and at the whole-cell level was similar in slgA mutants and controls. Thus, proline oxidase does not play a major role in generating neuronal glutamate pools at the Drosophila larva l neuromuscular junction, and larval neuromuscular performance is not alter ed significantly in slgA mutants. Metabolic pathways other than that involv ing proline oxidase are able to sustain glutamatergic synaptic function in Drosophila larvae.