St. Jude Researchers Discover Receptors That Bind to Reelin
This process is needed for correct development of the brain.
MEMPHIS, TENN., October 21, 1999 - Researchers could be a step closer to understanding the genes that control development of the brain and their potential association with neurodegenerative disorders, due to a major discovery at St. Jude Children's Research Hospital. Published in today's issue of Neuron, scientists have discovered that two lipoprotein receptors bind to the protein made by the reelin gene. Reelin is a molecule that serves as a "guidepost" for the movement of brain cells during development.
Lipoprotein receptors are responsible for removing cholesterol from the blood and they are important for heart disease. However, two of the lipoprotein receptors, the very low-density lipoprotein receptor (VLDLR) and Apolipoprotein E receptor 2 (ApoER2), are present in the brain. The new results place these receptors in a signaling pathway controlled by Reelin.
"To our surprise, we found that Reelin binds directly to the receptor molecules VLDLR and ApoER2. This binding must take place for correct development of the brain," said Tom Curran, Ph.D., Chair of the Developmental Neurobiology Department at St. Jude. The St. Jude team also discovered that lipoproteins, such as apolipoprotein E which bind to lipoprotein receptors, inhibit the interaction of Reelin with VLDLR.
Curran and Gabriella D'Arcangelo, Ph.D., St. Jude Department of Developmental Neurobiology, are the lead authors on this study.
This report presents researchers with another link in the signaling pathway controlled by Reelin and it gives scientists a better understanding of the molecular bases of brain development. Because some of the components of the pathway have been associated with Alzheimer's Disease, the findings suggest new opportunities to investigate the role of the Reelin pathway in neurodegenerative disorders.
"I think the next step is to figure out whether there is a real connection between the Reelin pathway and Alzheimer's Disease or neurodegeneration because there are many indications that a connection might exist," said D'Arcangelo.
This work is a continuation of a series of studies, based on the 1995 discovery of the reelin gene by Curran and D'Arcangelo. They found that this gene makes a protein that is released by some cells in specific regions of the brain that organizes nerve cells into layers. The team realized that if the reelin gene or protein is missing cells get lost and they end up in the wrong position within the brain.
St. Jude Children's Research Hospital, in Memphis, Tennessee, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC). All St. Jude patients are treated regardless of their ability to pay. ALSAC covers all costs of treatment beyond those reimbursed by third party insurers, and total costs for families who have no insurance.
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