How the presynapse forms and functions”
Department of Molecular Pharmacology & Cell Biology, Leibniz Institute, Berlin, Germany
Abstract
Nervous system function relies on the polarized architecture of neurons, established by directional transport of pre- and postsynaptic cargoes. While delivery of postsynaptic components depends on the secretory pathway, the identity of the membrane compartment(s) that supply presynaptic active zone (AZ) and synaptic vesicle (SV) proteins is largely unknown. I will discuss our recent advances in our understanding of how key components of the presynaptic machinery for neurotransmitter release are transported and assembled focussing on our studies in genome-engineered human induced pluripotent stem cell-derived neurons. Specifically, I will focus on the composition and cell biological identity of the axonal transport vesicles that shuttle key components of neurotransmission to nascent synapses and on machinery for axonal transport and its control by signaling lipids. Our studies identify a crucial mechanism mediating the delivery of SV and active zone proteins to developing synapses and reveal connections to neurological disorders. In the second part of my talk, I will discuss how exocytosis and endocytosis are coupled to maintain presynaptic membrane homeostasis. I will present unpublished data regarding the role of membrane tension in the coupling of exocytosis and endocytosis at synapses. We have identified an endocytic BAR domain protein that is capable of sensing alterations in membrane tension caused by the exocytotic fusion of SVs to initiate compensatory endocytosis to restore plasma membrane area. Interference with this mechanism results in defects in the coupling of presynaptic exocytosis and SV recycling at human synapses.
Topics
Related Seminars
Finding Meaning in Memories
Daphna Shohamy and Ashok Litwin-Kumar bridge experimental and computational neuroscience to explain how the brain assigns significance to memories, how dopamine shapes memory-guided decisions, and…
Deciphering the Dynamics of the Unconscious Brain under General Anesthesia
Stanford Neurosciences Seminar Series talk by Emery Brown (Massachusetts Institute of Technology, Neuroscience Statistics Research Lab) on deciphering the dynamics of the unconscious brain under…
The Connectome in Use: From anatomical wiring to functional organization in the behaving C. elegans brain
Rani Borbara presents brain-wide recordings from more than 150 freely moving C. elegans to examine how anatomical connectivity becomes functional organization during behavior. Cross-animal models…
Related Job Opportunities
PhD Studentship: Mitochondrial Metabolism and Novel Therapeutic Strategies for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) (Fixed Term)
Supervisors: Professor Andrew Murray, Department of Physiology, Development and Neuroscience, University of Cambridge Dr Ross Lindsay, Novo Nordisk Funding: Fully funded PhD studentship (Home/UK…
Postdoctoral Scientist - Sarvestani Lab
The Sarvestani Lab at Cornell University is recruiting a postdoctoral scientist in systems neuroscience to study how visual and motor systems across the brain and body support perception and…
ARISE2 Postdoctoral Fellowship - 2026 Call for Applications
EMBL's ARISE2 programme offers more than 20 fully funded, three-year postdoctoral fellowships for scientists developing research-infrastructure technologies across the life sciences, including…