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Nerve cells with stoppage: Evidence for a molecular key step in the process of signal transduction between nerve cells

By eliminating a single synaptic protein, German and US-american researchers provide the first direct evidence that vesicles, which act as cellular transporters, underlie a maturation process making them competent for membrane fusion in the context of neurotransmitter release at nerve cell synapses (Nature, 29 July 1999).

Information in the brain is transmitted at synapses which are specialized contact zones between signal-sending and signal-receiving nerve cells. When stimulated, a sending nerve cell generates an electric signal (the action potential) that travels along a spezialized cell process (the axon) to the synapse. There, the arriving signal triggers the release of neurotransmitter molecules, which now diffuse to the signal-receiving nerve cell, and change its physiological state.

A large number of proteins is involved in this complex cellular process. They regulate the turnover of the small cellular transporters known as vesicles, which first store the neurotransmitter molecules and then upon stimulation release them by fusing with the synaptic cell membrane (Figure 1). Under resting conditions nerve cells remain responsive because each of their synapses maintains a pool of transmitter-filled vesicles which are competent for membrane fusion and therefore can release neurotransmitter immediatly in response to an arriving action potential. To get fusion competent the vesicles run a maturation reaction which is analogous to the cocking of a gun, and represents a key step in the process of neurotransmitter release. Vesicle maturation has been inferred from numerous experimental observations but up to now was never demonstrated directly.

Iris Augustin in the laboratory of Nils Brose at the Max Planck Institute for Experimental Medicine in Goettingen/Germany generated mutant mice lacking a single synaptic protein, Munc13-1. In close collaboration with the electrophysiologist Christian Rosenmund of the Max Planck Institute for Biophysical Ch
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Contact: Nils Brose
brose@mail.mpiem.gwdg.de
4-9551-3899-725
Max-Planck-Gesellschaft
29-Jul-1999


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