The hustle and bustle inside cells is like life in the big city, with endless streams of vehicles trying to get their passengers and cargo to their important destinations. But there is a method to what may seem like madness, and scientists led by Ron Vale are analyzing the intracellular commute system right down to the tiny motor proteins that power the continuous transit.

Nature's tiniest motors - less than one-millionth of an inch - also are efficient and speedy machines, moving at 100 body lengths per second, which is faster than a race car. They are like car engines, but instead of relying on gasoline they convert chemical energy in the cell into physical movement. Muscle fibers in the human body, for example, are made up of billions of motor proteins all working together to generate the force that gives us our motion.

Life depends on these micromachines. Kinesin, the smallest of these motors and first identified in 1985 by Vale, a cell biologist, moves protein building blocks from their origin to far reaches in the cell and triggers the separation of genetic material during cell division. And ever since Vale learned that kinesin propels its biological cargo on microtubules - long-stranded structures that make up the roadways of the cells - he has devoted his research to studying this fascinating transport system.

Vale, professor of cellular and molecular pharmacology and an investigator for the Howard Hughes Medical Institute, was elected to the prestigious National Academy of Sciences in 2001 for his studies of molecular motors.

"The kinesin motors responsible for this transport are the world's smallest moving machines, even the smallest in the protein world," he said. "So, besides their biological significance, it's exciting to understand how these compact machines, many orders of magnitude smaller than anything humans have produced, have evolved that ability to generate motion."

Vale and his team of scientists, including postdoctoral fellows and graduate students, will take their research to the Mission Bay campus as part of the Institute for Quantitative Biomedical Research (QB3).

In recent years, Vale's laboratory has gone far beyond observing molecular traffic flow. It has devised techniques to analyze the behavior of single proteins. Instead of hundreds of different revved-up car engines on a highway, they can concentrate on the unique features of one.

"When examining the output of millions of motors, the mechanical events executed by individual molecular machines became blurred, since all work asynchronously," says Vale. "Now, single molecule analysis is revealing the actions of proteins that, until recently, were unknown."

And studying kinesin and other motor proteins for specific information on their velocity and force may also shed light on protein-to-protein interactions in general - how they bind and recognize each other, for example, to carry out the many tasks that make our bodies work.

Vale's laboratory has custom-built microscopes to study the dynamic properties of single kinesins. One uses a laser as an "optical tweezer" to trap, hold and move motors and observe how much force they produce.

Another microscope can detect the light emitted from a fluorescent dye molecule to image and track single motor proteins moving along the microtubule.

Vale has used these techniques to reveal how kinesin motors work as a team to haul their cargo - up to a thousand times their own size.

His lab is now attempting to engineer new kinesin motors with various velocities to test their theories on how kinesin works. As more is learned about motor proteins, clinical applications may follow. Inhibiting kinesins, for example, could interrupt the cell division involved in the runaway growth that causes cancer. Also, there is some indication that certain neurodegenerative diseases might be rooted in kinesin-related deficiencies in transport. A therapy could stimulate the motors involved in nerve transport to improve these diseases.

Another possible bonus from knowledge of these motors: Because the proteins are the best engines anywhere, engineers can learn from nature's mini-motors and build important microdevices for non-biological uses.

Source: Andy Evangelista

Links:
Ron Vale Lab
Animated model of processive motion by conventional kinesin

Last updated January 28, 2005

Ron Vale, professor of cellular and molecular pharmacology and an investigator for the Howard Hughes Medical Institute, first identified kinesin, tiny motor proteins inside cells.

Animated model of processsive motion by conventional kinesin
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Cellular microtubules

Kinesin, tagged in green fluorescence, traveling on microtubule