Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify botox receptor

29.09.2003


As doctors tout the toxin found in Botox for its ability to iron out wrinkles, calm muscle spasms and treat migraine headaches, defense agencies condemn it as a weapon that could wipe out large numbers of civilians.



While it is well known that this toxic substance can paralyze the body’s muscles, including the ones that help us breathe, how it infiltrates cells to do this has not been determined.

In a paper published in the Sept. 29 issue of the Journal of Cell Biology, researchers from the University of Wisconsin-Madison answer this long-standing question. They identify a receptor - a route of entry - for the Botox toxin that could lead to improved uses of the substance in the medical field and new methods for neutralizing it in the event of biological warfare.


Botulinum neurotoxin - the toxin found in Botox - is the deadliest of all substances. Produced by different strains of a family of bacteria, it comes in seven forms, four of which are reported to cause the paralyzing and potentially fatal disease of botulism. Currently, the family of bacteria that produces these toxins is listed by the Centers for Disease Control and Prevention as having the greatest potential for mass casualties if used as a biological weapon.

"Botulism is an old disease," says Edwin Chapman, a UW-Madison physiology professor and senior author of the new paper. "We know how the toxins block the release of neurotransmitters from neurons, but we didn’t know how they entered the neurons in the first place."

Whether inhaled or injected, the deadly toxins head straight for neurons, or nerve cells. Via a binding receptor on the surface of these cells, the toxins are brought inside where they block the release of neurotransmitters, chemicals that control muscle contraction and relaxation.

"The way they kill," explains Chapman, "is by inactivating the diaphragm so you no longer can draw a breath."

The receptor that pulls the toxins inside the nerve cells has puzzled scientists. Chapman says researchers have known that gangliosides - a special type of lipid - and proteins work together as a receptor, but no one until now has been able to identify the specific proteins.

Using a cellular model, Chapman, physiology and neuroscience graduate student Min Dong and others identified two proteins that function alongside gangliosides as the receptor for botulinum neurotoxin B - one of the four types deadly to humans. The proteins are synaptotagmin, or syt, I and II, which are found in certain types of neurons.

When one of these two proteins extends itself outside the cell during a process called exocytosis, the toxin latches on and then is internalized during the process of endocytosis.

To confirm that this protein and lipid pair is the actual physiological target of the toxin once it enters the body, the Wisconsin researchers set aside cell cultures and turned to a live mouse model. Working with their colleagues, Michael Goodnough and Eric Johnson in the Department of Food Microbiology and Toxicology, the researchers once again found that the toxin binds to and enters the cell via these two proteins and gangliosides.

"Our study is the first to identify a receptor for one of the botulinum neurotoxins and establish its entry route," says Dong, first author of the paper. "This knowledge will improve both the medical application of the [neurotoxin] and the prevention of a [biological] threat."

Knowledge of this receptor already had led to new research findings that suggest a possible antidote for the toxin.

As described in the paper published September 29, Dong has developed decoys that effectively neutralize one type of the neurotoxin. Specifically, he created fragments of the syt II protein that contain the toxin’s binding site.

In collaboration with Goodnough and Johnson, these fragments, along with gangliosides, were injected into the bloodstream of mice recently exposed to the toxin. The researchers found that the fragments neutralized most of toxic substance; injecting the fragments one minute prior to exposure neutralized 70 to 80 percent of the toxin.

As Chapman explains, "The fragments are a protective agent - a scavenger - that prevents the toxin from reaching its target."

These findings, says Dong, not only confirm the results from the cell culture studies but also provide some of the first evidence that identification of the receptor could play an integral role in developing measures that counteract the bacterial toxin, thereby safeguarding human lives against exposure to the lethal poison.

The fragment composed of the syt II protein is being patented by the Wisconsin Alumni Research Foundation, a non-profit agency that manages intellectual property for UW-Madison.

Currently, Dong and others are working to identify receptors for the other types of botulinum neurotoxin fatal to humans.


CONTACT:
Min Dong, 608-263-4166, mdong@wisc.edu
Edwin Chapman, 608-263-1762, chapman@physiology.wisc.edu
Emily Carlson 608-262-9772, emilycarlson@wisc.edu

Min Dong | idw
Further information:
http://www.wisc.edu/

More articles from Health and Medicine:

nachricht Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>