Study on Nerve Cell Development May Hold Clues to Alzheimer’s Treatments

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St. Louis, May 17, 2000 – Ann Marie Craig, Ph.D., an associate professor of anatomy and neurobiology at Washington University School of Medicine in St. Louis and a Pew Scholar in the Biomedical Sciences, has received a five-year $1.5 million grant from the National Institute of Neurological Disorders and Stroke. Craig is determining how proteins reach their correct sites in nerve cells.

Understanding protein trafficking in nerve cells could advance treatments for injury and Alzheimer’s disease, where this process is disturbed. Identifying molecules that target proteins to axons or dendrites also may be useful for gene therapy and other applications that need to direct proteins to particular cellular locations.

To investigate protein targeting, Craig is studying a family of membrane proteins called metabotropic glutamate receptors. These receptors bind the neurotransmitter glutamate, resulting in signaling between pairs of cells. Different family members have related structures but activate different signaling pathways. Whereas some members function in dendrites, others function in axons.

Nerve cells have branches called dendrites that receive information and branches called axons that pass information to other cells. Different complements of proteins and other cellular constituents account for this polarity.

Craig and former graduate student Julia Stowell discovered that a receptor’s tail serves as its admission ticket to the correct part of the cell, just as a ticket to New York gets a passenger on the right plane. Craig and postdoctoral associate Hélène Boudin, Ph.D., now will determine which part of a receptor makes it cluster within axons or dendrites at contact sites.

A second project will focus on the membranous sacs that transport proteins to dendrites or axons. The researchers will determine how many types of vesicles there are, look for associated components that direct them, and find out whether vesicles deliver their cargo into the cell’s outer membrane only at certain sites.

A third project will identify proteins that interact with traffic signals and might help package, transport and anchor the receptors. The role of specific molecular

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