A tale of two genes affecting synaptic structure and function

The synapses that neurons make with each other form the cellular basis of complex processes, such as thinking and learning. It is difficult to study molecular pathways responsible for synapse development, structure and function in a complex brain with millions of neurons making billions of connections with each other. We have utilized the powerful genetic tool of Drosophila melanogaster neuromuscular junction synapses, which like mammalian central synapses, are glutamatergic in nature. Using forward genetics screen, we found 2 different mutations that affect the synapses.

Mutation in tuberous sclerosis 2 (tsc2) gene leads increase in number of synapses and reduces the probability of neurotransmitter release per synapse. Using elegant genetics and molecular tools, we show that TSC2 functions via TORC2/AKT pathway to restrict the size of the synaptic terminus.

Mutation in protein kinase CK2 leads to accumulations of presynaptic active zone proteins in the axons. Ruling out the possibility of axonal transport defect, we show that CK2 is a novel regulator of transcription of active zone proteins with important functional implications that will be discussed during the presentation.