But understanding how the toxin -- one of seven neurotoxins produced by the bacterium Clostridium botulinum -- enters nerve cells has proved elusive for scientists. Despite a decade-long search for the receptor by labs around the world, researchers had come up empty handed.

Now, a research team led by Howard Hughes Medical Institute (HHMI) researcher Edwin R. Chapman reports that it has identified the cellular receptor for botulinum neurotoxin A. The group's work was published in the March 16, 2006, edition of ScienceXpress, which provides electronic publication of selected Science papers in advance of print. The finding offers important new insights that suggest how the toxin shuts down nerve cells with deadly efficiency.

In the clinic, the toxin, which is also known as botox, is used to treat forehead wrinkles, migraine headaches, urinary retention, eye muscle disorders, and excessive sweating. The same toxin also has more nefarious uses, and is considered a potential bioterror threat because it can kill people by paralyzing motor nerves in diaphragm muscles, causing breathing to stop. Lack of knowledge about the identity of the cell surface receptor that botulism toxin A uses to invade nerve cells has hindered the development of new antidotes to the toxin.

"People thought that since these were the most potent toxins known to humans, it would be easy to find the receptors," said Chapman, whose HHMI laboratory is at the University of Wisconsin-Madison. However, only a handful of proteins had been identified that appeared to interact with the toxin. But none of these proteins turned out to be the receptor, he said.

According to Chapman, researchers had long known how botulinum neurotoxin A attacks the nerve cell's internal molecular machinery.
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
16-Mar-2006