Molecular mechanisms that control synapse number and activity

Resumen

Synapse contacts are the primary form of communication between neurons. In this work, we explore how synapses are created, maintained and dismantled. We studied three different signaling mechanisms which induce changes at the larval neuromuscular junction of Drosophila melanogaster. We focused on two major aspects of neural function, synapse number and transmission. The study on PI3K signaling has revealed the functional hierarchical order of up- and down-stream components of the pathway. In addition, that study uncovered a second, antagonistic signaling pathway. Elements of the pro- and anti-synaptogenic pathways cross-regulate each other suggesting that the actual number of synapses that a neuron establishes results from a delicate equilibrium between synapse formation and elimination. The second study which composes this PhD project addresses the functional interaction between the Guanine Exchange Factor Ric8a and the calcium sensor Frq2, known in vertebrates as NCS-1. It describes how these two proteins contribute to determine the number of synapses and the probability of neurotransmitter release per synapse. Interestingly, these two synaptic features are regulated in opposite directions by the interaction Ric8a/Frq. Finally, the third study relates to Orb2, a protein involved in learning and memory in the adult, which acts as a pro-synaptogenic signal during developmental stages. Orb2 induces local translation of one of its target mRNA, the one that encodes the transcription factor Brat, through its structural transition from monomer (repressor) to oligomers (activator). Finally, Brat modulates synapse number, presumably through the regulation of genes encoding synapse components