unc-25 encodes the C. elegans ortholog of the GABA neurotransmitter biosynthetic enzyme, glutamic acid decarboxylase (GAD); unc-25 activity is required for GABA synthesis and thus for normal synaptic transmission and GABA-mediated behaviors; UNC-25 is expressed specifically in the 26 GABAergic neurons as soon as they are generated and localizes to cell bodies, axonal branches, and synaptic regions, including some localization to synaptic vesicles; in the 19 type D GABAergic neurons, unc-25 expression is positively regulated by the UNC-30 homeodomain transcription factor, which binds to the unc-25 promoter in a sequence-specific manner.
Predicted to enable glutamate decarboxylase activity and pyridoxal phosphate binding activity. Involved in GABAergic synaptic transmission. Located in axon; perikaryon; and synapse. Expressed in EF neuron and neurons. Used to study alcohol use disorder; epilepsy; and spastic cerebral palsy. Human ortholog(s) of this gene implicated in several diseases, including bipolar disorder; developmental and epileptic encephalopathy 89; and diabetes mellitus (multiple). Is an ortholog of human GAD1 (glutamate decarboxylase 1) and GAD2 (glutamate decarboxylase 2).
Mutations in Glutamic acid decarboxylase (GAD1), the human ortholog of elegans unc-25, are associated with autosomal recessive spastic cerebral palsy, a movement disorder caused by abnormalities in the brain; studies in elegans show that unc-25 is required for gamma-amino-butyric acid (GABA) synthesis and GABA-mediated behavioral functions; various GABA mutants in elegans, like unc-25, the GABA vesicular transporters (unc-46 and unc-47), and the GABA-A receptor, unc-49, all present head-bobbing convulsions.