Structure-building cell signals also may influence learning, memory

April 10, 2005

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 endocytosis 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 developmental neurobiology at Burnham. Pasquale is an internationally known expert in ephrins and their receptors, and Yamaguchi and Pasquale have been collaborating for more than 5 years to elucidate the function of ephrins and their receptors in nerve cells.
-end-
The research was supported by a grant from the National Institutes of Health.

The Burnham Institute, founded in 1976, is an independent not-for-profit biomedical research institution dedicated to advancing the frontiers of scientific knowledge and providing the foundation for tomorrow's medical therapies. The Institute is home to three major centers: the original Cancer Center, the Del E. Webb Neuroscience and Aging Center established in 1999, and the Infectious and Inflammatory Disease Center dedicated in 2004. Since 1981, the Institute's Cancer Center has earned the prestigious designation as a Non-comprehensive Cancer Center by the National Cancer Institute. Discoveries by Burnham scientists have contributed to the development of new drugs for Alzheimer's disease, heart disease and several forms of cancer. Today the Burnham Institute employs over 700, including more than 550 scientists. The majority of the Institute's funding derives from federal sources, but private philanthropic support is essential to continuing bold and innovative research. For additional information about the Institute and ways to support the research efforts of the Institute, visit www.burnham.org.

Sanford-Burnham Prebys Medical Discovery Institute

Related Memory Articles from Brightsurf:

Memory of the Venus flytrap
In a study to be published in Nature Plants, a graduate student Mr.

Memory protein
When UC Santa Barbara materials scientist Omar Saleh and graduate student Ian Morgan sought to understand the mechanical behaviors of disordered proteins in the lab, they expected that after being stretched, one particular model protein would snap back instantaneously, like a rubber band.

Previously claimed memory boosting font 'Sans Forgetica' does not actually boost memory
It was previously claimed that the font Sans Forgetica could enhance people's memory for information, however researchers from the University of Warwick and the University of Waikato, New Zealand, have found after carrying out numerous experiments that the font does not enhance memory.

Memory boost with just one look
HRL Laboratories, LLC, researchers have published results showing that targeted transcranial electrical stimulation during slow-wave sleep can improve metamemories of specific episodes by 20% after only one viewing of the episode, compared to controls.

VR is not suited to visual memory?!
Toyohashi university of technology researcher and a research team at Tokyo Denki University have found that virtual reality (VR) may interfere with visual memory.

The genetic signature of memory
Despite their importance in memory, the human cortex and subcortex display a distinct collection of 'gene signatures.' The work recently published in eNeuro increases our understanding of how the brain creates memories and identifies potential genes for further investigation.

How long does memory last? For shape memory alloys, the longer the better
Scientists captured live action details of the phase transitions of shape memory alloys, giving them a better idea how to improve their properties for applications.

A NEAT discovery about memory
UAB researchers say over expression of NEAT1, an noncoding RNA, appears to diminish the ability of older brains to form memories.

Molecular memory can be used to increase the memory capacity of hard disks
Researchers at the University of Jyväskylä have taken part in an international British-Finnish-Chinese collaboration where the first molecule capable of remembering the direction of a magnetic above liquid nitrogen temperatures has been prepared and characterized.

Memory transferred between snails
Memories can be transferred between organisms by extracting ribonucleic acid (RNA) from a trained animal and injecting it into an untrained animal, as demonstrated in a study of sea snails published in eNeuro.

Read More: Memory News and Memory Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.