#IDIBELLseminars: UNC13A: From a SNAREopathy to Neurodegeneration

Intact communication between neurons occurs at synapses and is absolutely essential for information processing in neuronal networks. A massive body of work draws a link between genetic variations in synaptic proteins and complex brain disorders, but the mechanisms by which synaptic transmission is altered to product disease are not well-understood. Munc13 proteins are key regulators of neurotransmitter release, as they mediate the priming step that renders synaptic vesicles fusion-competent. I will present data describing a novel congenital brain disorder of the synaptic vesicle priming step, characterized by autism-spectrum disorder, a dyskinetic movement disorder, and intellectual disability. Our study underscores the critical importance of fine-tuned presynaptic control in normal brain function, and adds the neuronal Munc13 proteins and the synaptic vesicle priming process to the known etiological mechanisms of neurological disease.

Hosted by Francisco José López-Murcia – Cellular and Molecular Neurobiology group

Noa completed her PhD in collaboration between the labs of Dr. Uri Ashery at Tel Aviv University and Prof. Nils Brose at the Max Planck Institute of Experimental Medicine in Göttingen, combining mouse genetics and electrophysiology to study synaptic signaling pathways that control short-term synaptic plasticity. As a postdoc she continued these studies and characterized a new inborn brain disorder associated with variations in the UNC13A gene. Since 2020 she leads the Junior Research Group ‘Synapse Biology’ at the LeibnizFMP. Her group combine genetic manipulations in mouse models with electrophysiological and cell type-specific proteomics to study the molecular code that defines synaptic function and plasticity