Biophysical Society Conference | Estes Park 2023

Membrane Budding and Fusion

Wednesday Speaker Abstracts

HUMAN UNC13A GENE VARIATIONS CAUSE A NEURODEVELOPMENTAL SYNDROME AND IMPAIR SYNAPTIC FUNCTION Reza Asadollahi 4,5 ; Aisha Ahmad 1,2 ; Jasmine Shahanoor 3 ; Paranchai Boonsawat 4 ; Siqi Sun 1 ; Mareike Lohse 1,2 ; Muragash Padmanarayana 3 ; Holger Taschenberger 2 ; Nils Brose 2 ; Jonas Sommer 1 ; Jeremy Dittman 3 ; Anita Rauch 4 ; Noa Lipstein-Thoms 1,2 ; 1 Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Molecular Physiology and Cell Biology, Berlin, Germany 2 Max Planck Institute of Multidisciplinary Sciences, Molecular Neurobiology, Göttingen, Germany 3 Weill Cornell Medicine , Biochemistry, New York, NY, USA 4 University of Zurich, Institute of Medical Genetics, Zurich, Switzerland 5 University of Greenwich, Biology and biomedical science, London, United Kingdom 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 are not well-understood. At the presynaptic compartment, hundreds of proteins act together to determine the strength, timing, and plasticity of neurotransmitter release, thus shaping the properties of synaptic transmission. Of those, UNC13 proteins are key regulators of neurotransmitter release, as they mediate the priming step that renders synaptic vesicles fusion-competent. Here, we describe a novel congenital brain disorder of the synaptic vesicle priming step, characterized by autism-spectrum disorder, a dyskinetic movement disorder, and intellectual disability. We identified disease-related variations in the UNC13A gene, and carried an electrophysiological characterisation that identified mechanisms leading to synaptic transmission dysfunction. 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 psychiatric and neurological disease.

SPATIAL AND TEMPORAL REGULATION OF CONSTITUTIVE EXOCYTOSIS IN CELL SHAPE CHANGE

Stephanie L. Gupton ; 1 University of North Carolina at Chapel Hill, Cell Biology and Physiology, Chapel Hill, NC, USA

The constitutive fusion of secretory vesicles to the plasma membrane is a driving factor in cellular shape change in many cell types. Our work has investigated the spatial and temporal occurrence of vesicle fusion in developing neurons as a means of plasma membrane expansion during the dramatic increases in surface area during neuronal morphogenesis. We are developing tools to image and analyze the fusion of multiple vesicle types across multiple cell types, shape changes, and manipulations. Here we discuss how the organization and regulation of vesicle fusion depends on vesicle type and cell type, revealing general principles and specificities.

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