La Jolla, Calif. A Burnham Institute study has found that one of the cell's largest families of signaling molecules, called ephrins, which are known to regulate the development of nerve cells, also controls nerve cells' ability to engulf critical chemicals and proteins for learning and memory. These findings, the first to link these molecular semaphores to this important nerve cell function, appear in the May issue of Nature Cell Biology, published in advance at the journal's website on April 10th.

While the study's results are not immediately applicable to treating disease, they pave the way for future experiments on the roles played by ephrins in memory, learning, and other nerve cell functions, and potentially even in certain cancers.

By inserting chicken ephrin genes into rat cells, Fumitoshi Irie, Ph.D., Professor Yu Yamaguchi, M.D., Ph.D., and their colleagues found that when the ephrin subtype EphrinB activated its EphB receptor, a cascading chemical pathway was triggered that ultimately stimulated an enzyme called synaptojanin-1. This enzyme is essential for a process known as cellular endocytosis, whereby certain chemicals, viruses or other agents are surrounded with a snippet of the cell's membrane. Endocytosis important as it is the process by which cells take up materials such as neurotransmitters, fat molecules, and foreign bodies like viruses and toxins, from the external environment thus enabling the cell to store, transport or eliminate these materials.

Synaptojanin-1 enables endocytosis when it disassembles a molecular coating on storage vesicles, which allows the cell to continue making new vesicles as needed. "This was a new pathway for ephrin," said Yamaguchi. "Ephrin has been intensively studied for many years, with most attention being paid to its maintenance of the cell's skeletal structure during development."

Once the biochemical pathway was determined, the researchers then looked at whether ephrin truly increased end
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Contact: Nancy Beddingfield
nbeddingfield@burnham.org
858-646-3146
Burnham Institute
10-Apr-2005

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