Roller coaster riders inside cells
SCIENTISTS are discovering that specialised structures in the minute world of cells do not float randomly from place to place but are actively transported along well laid out tracks by a veritable menagerie of motor molecules (Science, Vol 256 No 5065).
The motor molecules play a fundamental role in the cell's activities. They guide the migration of small vesicles that carry enzymes to nerve terminals where impulse-transmitting substances -- neurotransmitters -- are made and released, and propel into place protein filaments required to construct structures such as the endoplasmic reticulum, where proteins are assembled. They are also thought to help separate chromosomes during cell division, when each of the two daughter cells that are formed gets a copy of every chromosome.
These molecules are of more than theoretical interest because they could explain the sometimes abnormal movements of chromosomes during cell division that result in abnormalities underlying cancer development, other genetic disorders like Down's syndrome and certain types of infertility.
Ever since British scientists Andrew and Hugh Huxley recognised, some 40 years ago, that muscle contractions are brought about when two protein filaments -- one comprising myosin molecules and the other actin -- slide past each other, scientists have been trying to crack how movements within cells take place.
A breakthrough in motor molecule research, however, came in 1982, when Michael Sheetz, now at Duke University, and James Spudich's team at Stanford University, were trying to determine if the actin fibres -- which appeared to have polarity because its subunits collected more rapidly at one end -- influenced the direction of myosin movement.
Myosin heads are too small to be seen with a light microscope, and although high-resolution electron microscopy enables observation of myosin and actin structures, it does not help in scrutinising their movements as material has to be "fixed" or inactivated. So, the scientists attached the myosin protein to small plastic beads that could be seen with a light microscope and watched what happened when the beads were put in contact with actin fibres in cells from the Nitella axillaris plant.
Sheetz and Spudich's tracking experiments revealed the beads travelled only in one direction, suggesting myosin movement was dictated by the polarity of actin.
Using the revolutionary technique developed by Sheetz and Spudich's team, researchers discovered that what help transport neurotransmitter vesicles from the nerve cell body to the nerve terminals are not actin filaments as they expected, but tubulin, another protein. Tubulin did not direct the movement of myosin but interacted with another protein called kinesin, first isolated by researchers in 1985 from squids. Plastic beads attached to kinesin travelled along tubulin tracks in much the same way as myosin travelled along actin filaments. It was later discovered the return journey of vesicles from the terminals to the cell body is powered by another protein called dynein.
In 1990, researchers linked motor molecules to cell division after dynein was found where transport filaments called microtubules are attached to chromosomes. Some researchers believe that during cell division, dynein molecules move the chromosomes toward the cell ends of the microtubules.
Though the necessity of motor molecules to facilitate movement within cells is recognised by scientists, few actually understand how these proteins actually work. Already, the notion that kinesin propels vesicular movement in one direction and dynein in the other has been abandoned after findings that the two proteins can work in both directions. With the constantly changing facts about molecule motors, says Tim Mitchison of the University of California in San Francisco, "the problem is getting more complex, not simpler."