UIC researchers show protein routes messages in nerve cells

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UIC researchers show protein routes messages in nerve cells

14 Jul 2005 Medical News Today

Nerve cells relay messages at blink-of-the-eye speeds by squirting

chemicals called neurotransmitters across tiny gaps called synapses

to awaiting message receptors. But lots of different receptors and

neurotransmitters work simultaneously. Which goes where to send the

proper message?

Research reported in the July 20 issue of the Journal of Neuroscience

(released online July 13) by a team led by Featherstone, a

University of Illinois at Chicago assistant professor of biology,

provides some important preliminary answers.

Featherstone and UIC post-doctoral associate Kaiyun Chen, along with

German researchers Merino and Stephan Sigrist at the European

Neuroscience Institute in Goettingen, chose the common fruit fly as

their research animal and the chemical glutamate -- present in fruit

flies and humans -- as their neurotransmitter of choice.

" It's still unknown how glutamate receptors get to precisely where

they're supposed to go on a cell in order to mediate the

neurotransmission, " said Featherstone. " If the receptors are not in

the right place, then the message becomes less efficient. Or if

receptors are the wrong type, the message could get completely mixed

up. "

Such mix-ups can lead to a condition called synaesthesia, where, for

example, a sound may have taste, or an image may have a smell. The

molecular basis of this condition remains unknown.

" It all comes down to the receptors being in the right place at the

right time, " said Featherstone. " So our question was, how do these

receptors know where they're supposed to go at the time they're

supposed to be there? "

Fruit flies proved to be ideal test animals for answering the

question because a synapse called the neuromuscular junction in the

fly works much like synapses in human brain cells.

" We can quickly mutate the flies, " said Featherstone. " We looked

among thousands of them for those without the glutamate receptors in

the right place at the right time. Then we knew that the gene we

mutated codes for a protein that is critical for getting those

receptors to the right place at the right time. "

Featherstone and his colleagues found that a protein called coracle --

known as 4.1 in humans -- links receptors on a nerve cell's membrane

to its internal structure, or cytoskeleton. Because 4.1 only

interacts with certain receptor proteins, it functions as a sorting

agent to ensure that only the correct type of receptor gets attached.

The work by the researchers also identifies the cytoskeleton proteins

to which the receptors are tied: actin.

" Many researchers have identified proteins that interact with

glutamate receptors, but there's never previously been a link found

to the cytoskeleton, " said Featherstone. " This work finally ties the

receptors to the cell framework to provide a complete picture. "

Confirmation of these mechanisms in a mammal such as a mouse or a rat

can help researchers understand how nerves need to be reconnected

after spinal cord injury, or may open doors to developing drugs that

can manipulate proteins that cause neurological diseases in humans.

Funding for this research was provided by the National Institute of

Neurological Disorders and Stroke, one of the National Institutes of

Health.

http://www.uic.edu