TY - JOUR

T1 - 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

AU - Shayan, A. J.

AU - Brodin, L.

AU - Ottersen, O. P.

AU - Birinyi, A.

AU - Hill, C. E.

AU - Govind, C. K.

AU - Atwood, H. L.

AU - Shupliakov, O.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - The sluggish-A (slg A) gene of Drosophila melanogaster has been shown to encode for the enzyme proline oxidase, a mitochondrial enzyme which catalyzes the first step in the conversion of L-proline to L-glutamate. The slg A transcript is expressed in both larval and adult Drosophila melanogaster. Mutations 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 neurotransmitter glutamate in the nervous system, a reduction in proline oxidase activity could reduce neural glutamate pools and affect synaptic transmission in neurons utilizing glutamate as a transmitter, including peripheral motor neurons. We tested the hypothesis that glutamate, and synaptic transmission mediated by glutamate, are reduced at synapses of glutamatergic motor neurons in slg A mutants. Levels of glutamate and proline in different cell compartments, and functional properties of synaptic transmission were compared in slg A and control specimens. Proline is elevated in muscle cells of slg A mutants, indicating that the slg A gene regulates tissue proline levels. In nerve terminal varicosities, proline levels were low in both mutants and controls. Glutamate levels in nerve terminal varicosities of slg A mutants and controls were similar. In addition, we found that glutamatergic synaptic transmission at individual nerve endings and at the whole-cell level was similar in slg A mutants and controls. Thus, proline oxidase does not play a major role in generating neuronal glutamate pools at the Drosophila larval neuromuscular junction, and larval neuromuscular performance is not altered significantly in slg A mutants. Metabolic pathways other than that involving proline oxidase are able to sustain glutamatergic synaptic function in Drosophila larvae.

AB - The sluggish-A (slg A) gene of Drosophila melanogaster has been shown to encode for the enzyme proline oxidase, a mitochondrial enzyme which catalyzes the first step in the conversion of L-proline to L-glutamate. The slg A transcript is expressed in both larval and adult Drosophila melanogaster. Mutations 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 neurotransmitter glutamate in the nervous system, a reduction in proline oxidase activity could reduce neural glutamate pools and affect synaptic transmission in neurons utilizing glutamate as a transmitter, including peripheral motor neurons. We tested the hypothesis that glutamate, and synaptic transmission mediated by glutamate, are reduced at synapses of glutamatergic motor neurons in slg A mutants. Levels of glutamate and proline in different cell compartments, and functional properties of synaptic transmission were compared in slg A and control specimens. Proline is elevated in muscle cells of slg A mutants, indicating that the slg A gene regulates tissue proline levels. In nerve terminal varicosities, proline levels were low in both mutants and controls. Glutamate levels in nerve terminal varicosities of slg A mutants and controls were similar. In addition, we found that glutamatergic synaptic transmission at individual nerve endings and at the whole-cell level was similar in slg A mutants and controls. Thus, proline oxidase does not play a major role in generating neuronal glutamate pools at the Drosophila larval neuromuscular junction, and larval neuromuscular performance is not altered significantly in slg A mutants. Metabolic pathways other than that involving proline oxidase are able to sustain glutamatergic synaptic function in Drosophila larvae.

KW - Glutamate

KW - Immunolocalization

KW - Motor neuron

KW - Muscle

KW - Synapse

KW - Ultrastructure

UR - http://www.scopus.com/inward/record.url?scp=0033892120&partnerID=8YFLogxK

U2 - 10.3109/01677060009083481

DO - 10.3109/01677060009083481

M3 - Review article

C2 - 10992167

AN - SCOPUS:0033892120

VL - 14

SP - 165

EP - 192

JO - Journal of Neurogenetics

JF - Journal of Neurogenetics

SN - 0167-7063

IS - 3

ER -