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Structure-building cell signals also may influence learning, memory

ocytosis in cells that were not altered genetically. Using rat brain cells, they found that increased signaling did indeed create more vesicles in normal cells. Most important, these new vesicles were important parts of nerve cell synapses, the sophisticated communication relay used in the nervous system.

"We looked at the glutamate receptors at the cell synapse, and depending on other activity, ephrin appeared to decrease the number of glutamate receptors," said Yamaguchi. The regulation of glutamate receptors is crucial to maintaining memory and learning. The strength of a signal through a nerve cell synapse can be enhanced (by increasing the number of receptors) or diminished (by a receptor decrease). "The balance has to be optimal, since too much memory activation can also be a problem," said Yamaguchi.

Yamaguchi's team, which worked on this project for more than two years, had suspected that ephrins played some important part in nerve cell synapse function. Previous studies had shown that animals injected with addictive drugs had activated EphB receptors, and that there is a connection between synaptojanin-1 and bipolar disorders and schizophrenia. Until now, nobody had made the connection between EphB and the endocytosis involved in neurotransmitter regulation.

"There's also an increased interest in endocytosis in cancer, in which the process may help diminish anti-proliferation signals and, as a result, trigger tumor progression," said Yamaguchi. "But this is a novel finding in biology, and we can only just begin to speculate on the broader implications of Ephrin and EphB's activity."

Yamaguchi is a professor of developmental neurobiology at the Burnham Institute, where his research zeros in on the structure and activity of nerve cell synapses. Irie, the lead author of the paper, is a staff scientist in Yamaguchi's laboratory. Their colleagues included Misako Okuno in Yamaguchi's laboratory and Elena Pasquale, who also is a professor of
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Contact: Nancy Beddingfield
nbeddingfield@burnham.org
858-646-3146
Burnham Institute
10-Apr-2005


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