nerve synapses: Protein synthesis can be controlled by light, opening way for ne

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Protein synthesis can be controlled by light, opening way for new

scientific, medical applications

25 Jun 2005 Medical News Today

Proteins are the puzzle-pieces of life, involved in how organisms

grow and flourish, but studying their complex biological processes in

living systems has been extremely difficult. Now, a team of chemists

and neurobiologists led by Dore at the University of Georgia

and M. Schuman at the California Institute of Technology has

found a way to use light to regulate protein synthesis in specific

locations.

The new method, which uses so-called " caged compounds " that can be

turned on with light, could lead to more intricate studies of such

important but poorly understood processes, such as protein synthesis

in nerve synapses.

The research was published today in the journal Chemistry & Biology.

Coauthors on the paper are Schuman, Goard, Girish Aakalu,

Carlo Quinonez and Jamii St. n, all of the Medical

Institute and Division of Biology at the California Institute of

Technology. Lesya Fedoryak from Dore's lab is also an author of the

paper, as is Poteet, now a medical student at the University

of Alabama, Birmingham, who participated in UGA's Chemistry Summer

Undergraduate Research Program in 2001.

The idea of " caged compounds " has been around for some 30 years. In

the current application, the team attached a light-sensitive molecule

called a chromophore to a bioactive molecule called an effector

through a single covalent bond that inactivates the bioactive

molecule. Exposing the caged compound to light releases the effector

in its active form.

" It's analogous to placing an animal in a cage to restrict its

activity, " said Dore, " but the term 'cage' is really a misnomer

because we are not actually placing a molecule inside of a molecule. "

The team developed a caged anisomycin compound that can be activated

by exposure to ultraviolet light or an infrared laser beam.

(Anisomycin is an antibiotic that inhibits protein synthesis.) The

new chromophore, called Bhc, is the only one sensitive enough to

light that it can mediate light-induced protein synthesis inhibition

in a living system.

While previous studies have focused on releasing molecules that

activate biological events, little has been done in the area of

regulating the inhibition of biological processes.

" Ultimately, we want to understand the role local protein synthesis

plays in biological systems such as neurons, " said Schuman. " When and

where in the neuron is protein synthesis used to bring about changes?

How does protein synthesis regulate synaptic strength and axonal

outgrowth? These are questions we'd like to answer. "

Another example of a process the new method can help clarify involves

the role of protein synthesis in the development of an organism.

Since stem cells in humans, for example, differentiate into skin,

brain and muscle cells, among many others, researchers want to know

the controlling mechanisms for how these cells are chosen for their

specific roles.

" If we had a way to selectively abolish protein synthesis in

subcellular compartments and observe the effects, then we could infer

the role of local protein synthesis in development, " said Dore.

Generally speaking, there are few research tools available that are

location-specific, so the new method adds a potentially powerful tool

for scientists. Often, manipulations are carried out on all parts of

a sample, but researchers have learned that much of biological

function is dependent on the specific location of a particular event.

While the new caged compound and its photoreactive properties may

never be used for anything as complex as drug delivery, it may well

serve a purpose in studying such areas as memory, brain function and

even Alzheimer's Disease.

" Our technique will enable scientists to conduct experiments aimed at

understanding the mechanisms of learning and memory at the molecular

and cellular level, " said Dore.

The technique could also be used in drug discovery and development,

though it is much more likely to be used in advancing knowledge about

biological systems.

http://www.uga.edu