Feb. 12, 2009
CAPTION FOR LOWER RIGHT IMAGE: A migrating fibroblast shows active calcium flickers at the cell's leading edge (right side). A UI scientist helped solve a paradox about how these flickers help steer cells within the body. Credit: University of Iowa/Song Laboratory.
UI researcher helps catch 'calcium flickers' in action
Calcium doesn't only help build strong bones. It's essential to many biological functions, including muscle contraction, hormone secretion, learning and memory.
Now, a University of Iowa researcher has contributed to a recent study that helps show how calcium drives cells to move in the right direction. Because this directional cell movement is fundamental to such processes as tissue formation, wound healing and tumor metastasis, the finding could help lead to new treatments for human diseases.
The investigation was led by researchers at Peking University and appears in the Feb. 12 print issue of the journal Nature.
The study resolves a long-standing paradox about intracellular calcium in migrating cells, said study author Long-Sheng Song (photo, left), M.D., assistant professor of internal medicine at the UI Roy J. and Lucille A. Carver College of Medicine, who is a scientist with expertise in calcium imaging.
"Previous research indicated that intracellular calcium was more highly concentrated at the tail end, rather than at the leading edge, of migrating cells," Song said. "But because cells want to advance, the leading edge supposedly would require a higher concentration of calcium in order to influence the proteins that drive the cell to migrate."
The researchers used an advanced form of real-time, laser-scanning confocal microscopy that involves special illumination to view the calcium distribution in human embryonic lung fibroblasts (image, right). The new technology made a difference. They observed that, in fact, there was significant, although short-lived, highly localized calcium activity -- the so-called "calcium flickers" -- at the leading edge of the cell.
They then exposed the cells to a chemical that stimulates cell migration during wound healing. As the cells moved toward the chemical, the calcium flicker action increased and occurred in a special pattern. This suggests that calcium flickers steer cells in the right direction.
"More important, this study unmasked the molecular basis underlying the genesis of the calcium flickers, and it provides clues for future study of cell migration," Song said. "In turn, the research could provide direction for developing new therapies for human diseases."
Song came to the UI's Division of Cardiovascular Medicine two years ago from the University of Maryland, where he received training under W. Jonathan Lederer, M.D., Ph.D., a scientist recognized internationally for his discovery of calcium sparks in cardiac cells.
The study's senior author is Heping Cheng. He and Chaoling Wei are the study's corresponding authors. The two scientists completed part of the study at Song's lab while visiting the UI from their home institution in China.
The study was supported by the Major State Basic Research Development Program of China, the National Natural Science Foundation of China and a National Institutes of Health grant.
ABSTRACT: Nature,Vol 457, Number 7231, Feb. 12, 2009, http://www.nature.com/nature/journal/v457/n7231/abs/nature07577.html
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