Embargoed until 2:00 p.m. EDT
NSF PR 01-47 - May 30, 2001

Media contact:

Tom Garritano, NSF

(703) 292-8070

[email protected]

Program contact:

Monica Nadler,
BIDMC/HMS

(617) 667-3705

[email protected]

This material is available primarily for archival purposes. Telephone numbers or other contact information may be out of date; please see current contact information at media contacts.

Secret Channel Holds Key to Metabolic Mysteries
Researchers use cloned gene to reveal how cells transmit vital elements

Biologists have discovered a "channel" that allows key elements such as calcium and magnesium to enter living cells. The research, published in the May 31 issue of the journal Nature, provides new insight into the link between metabolic activity and a cell's ability to regulate its levels of key elements. This connection has been poorly understood despite its importance to human health.

The work was possible because Monica Nadler of Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS) in Boston cloned a particular gene while supported by a grant from the National Science Foundation's (NSF) Professional Opportunities for Women in Research and Education (POWRE).

Three separate teams of scientists, led by Nadler's BIDMC/HMS colleague Andrew Scharenberg, studied activity in the product of a gene called LTRPC7, which they found permits calcium ions to enter cells. In collaboration with Reinhold Penner of the University of Hawaii, they discovered that the channel is sensitive to the presence of a chemical complex of magnesium and a molecule called ATP. ATP has long been recognized as the primary energy carrier in living cells. The channel's sensitivity to the magnesium-ATP complex reveals a direct link between the LTRPC7 channel's ability to conduct calcium ions and the cell's energy level. The discovery of this relationship could have long-term implications for human conditions such as hypoxia (oxygen deficiency) and hypoglycemia (sugar deficiency).

"We had hoped the channel might be capable of passing calcium ions," Nadler said. "That proved to be the case. In collaboration with Tomohiro Kurosaki's group at Kansai Medical University in Osaka, Japan, we discovered that the gene has another surprising characteristic -- removing it proves 100 percent lethal to cells."

This is a further indication that the researchers are onto something important, because lethality shows that the gene is somehow essential to every cell's life. The Nature paper is important in part because it will stimulate a race to determine the gene's precise functions, and why no cell can live without it.

"LTRPC7 represents a new family of ion channels that have yet to be explored," Nadler said. "Importantly, we don't yet understand how ion channels transmit elements in relation to metabolic function. LTRPC7's lethality when lost means it has fundamental importance, so we need more research to explain it."

The NSF POWRE award helped Nadler keep her research active while raising two young daughters -- now ages two and three. "This grant gave me a chance to pursue my work while I was striving to achieve a critical balance between building my career and starting my family," she said.

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