Richard Scheller and Thomas Südhof receive the 2013 Albert Lasker Basic Medical Research Award

Abstract

Neural communication underlies all brain activity. It governs our thoughts, feelings, sensations, and actions. But knowing the importance of neural communication does not answer a central question of neuroscience: how do individual neurons communicate? We know that communication between two neurons occurs at specialized cell junctions called synapses, at which two communicating neurons are separated by the synaptic cleft. The presynaptic neuron releases chemicals, known as neurotransmitters, into the synaptic cleft in which neurotransmitters bind to receptors on the surface of the postsynaptic neuron. Neurotransmitter release occurs in response to an action potential within the sending neuron that induces depolarization of the nerve terminal and causes an influx of calcium. Calcium influx triggers the release of neurotransmitters through a specialized form of exocytosis in which neurotransmitter-filled vesicles fuse with the plasma membrane of the presynaptic nerve terminal in a region known as the active zone, spilling neurotransmitter into the synaptic cleft. By the 1950s, it was clear that brain function depended on chemical neurotransmission; however, the molecular activities that governed neurotransmitter release were virtually unknown until the early 1990s. This year, the Lasker Foundation honors Richard Scheller (Genentech) and Thomas Sudhof (Stanford University School of Medicine) for their “discoveries concerning the molecular machinery and regulatory mechanisms that underlie the rapid release of neurotransmitters.” Over the course of two decades, Scheller and Sudhof identified and characterized a set of proteins that mediate the fusion of neurotransmitter-filled synaptic vesicles with the plasma membranes of presynaptic nerve terminals. These proteins participate in the formation and regulation of a membrane-bridging complex, known as the soluble NSF attachment protein (SNAP) receptor (SNARE) complex. It is now known that this mechanism is used to mediate various forms of exocytosis throughout the body.