Small G-Proteins Make A Big Difference -- Nerve Cell Signalling Is Regulated By,,Arf-GTPases And Their Activators

Researchers at the Max Planck Institutes for Biophysical Chemistry and for Experimental Medicine in Göttingen/Germany discovered a new regulatory process through which nerve cells modulate the release of neurotransmitter in the brain (Proc. Natl. Acad. Sci. U.S.A. 96, 1094-1099; Feb. 2, 1999).

Information in the brain is transmitted at synapses which are specialized contact zones between a sending and a receiving nerve cell. When stimulated, the sending nerve cell releases signalling molecules. These so called neurotransmitters diffuse to the receiving nerve cell where they activate surface receptors that in turn change the physiological state of the receiving cell and thereby transmit the synaptic signal.

Transmitter release at synapses is a complex process. It involves a large number of proteins which regulate the turnover of synaptic vesicles, small membranous intracellular organelles that store neurotransmitter and release it upon stimulation by fusing with the cell membrane. In a nerve cell, synaptic vesicles pass through a sophisticated cycle of fusion and budding reactions, and the efficiency of these reactions determines the vesicle supply that is ready for transmitter release at any moment in time.

Uri Ashery and Volker Scheuss in the laboratory of Jens Rettig at the Max Planck Institute for Biophysical Chemistry, Göttingen/Germany, used a new method to identify two novel regulators of the synaptic vesicle cycle. In collaboration with Henriette Koch and Nils Brose, head of a research group at the Max Planck Institute for Experimental Medicine in Göttingen/Germany, they expressed the protein msec7-1 in neuromuscular synapses of Xenopus frogs. msec7-1 is an activator of members of the Arf-family of small GTPases. Both msec7-1 and Arfs are very prominent regulators of membrane transport in the Golgi apparatus of all cells in the body. The Göttingen group discovered that the msec7/Arf-system plays an as yet unrecognized

Contact: Jens Rettig, Nils Brose

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