Cell Cargo Speeds On Bidirectional Highways
As reported here numerous times (e.g., 06/14/2004, 12/04/2003, 04/14/2003, 03/28/2003, 02/25/2003, 12/17/2002, 09/26/2002, 03/26/2002, 02/01/2002, 12/06/2001, 08/17/2001, 06/19/2001, 02/21/2001), cells have an elaborate interstate highway system with molecular trucks hauling cargo back and forth. Scientists have known that the cellular highways have polarities labeled plus and minus, and that molecular motors typically go one way. Some motors, like kinesin, drive only in the plus direction, while others, like dynein, go in the minus direction. Now, it is becoming apparent that most pieces of cargo have at least one of each kind of motor, with a stickshift that allows it to drive in forward or reverse. The state of our knowledge about bidirectional transport is explored by Michael Welte in the July 13 issue of Current Biology.1
Welte examines the evidence that many, maybe all, moving cargoes have bidirectional ability. In the microscope, certain organelles like mitochondria and melanosomes are seen to move back and forth rapidly, eventually making it to their target. Why is this, and how is it done? Does the organelle grab motors out of the cytoplasm? Are both motors working in a tug-o’war? Welte cites evidence against these possibilities, and suggests (although hard evidence needs to be found), that the cargo carries both motors, and a “complex coordination machinery … ensures that when one motor is actively engaged with the microtubule, the other motor is turned off.” Moreover, this coordination machinery, whatever it is, may be under the influence of regulatory enzymes. “If the coordination machinery can attach to cargo independent of the motors,” he surmises, “distinct variants of the coordination machinery could be targeted to different cargoes, thus allowing cargo-specific coordination and regulation.”
It seems odd, though, that cargoes would undergo a back-and-forth random walk instead of making a beeline to the target. Welte figures there must be biological justification for this behavior, so he examines some possibilities:
- Economy: “If cargoes always carry motors for both directions, net transport can easily be adjusted or even reversed by simply tweaking the relative activity of the two motors. This is likely to be much quicker than assembling a new set of motors on a cargo, and also allows transport to be abruptly altered depending on cellular needs. It even makes it possible to tune the overall speed of transport by altering the relative contribution of trips in the non-dominant direction.”
- Setting Up Polarized Distributions: “Sometimes it is necessary to set up a distribution rather than to confine the organelles to a single point …. Even if cargoes accumulate at a certain point (e.g. near plus-ends when motion is biased in the plus-end direction), trips in the non-dominant direction will tend to spread the cargoes out along the tracks, away from the point of accumulation. Modeling shows that by altering the relative contributions of plus- and minus-end trips, a wide range of steep to flat steady-state distributions can be achieved.”
- Avoiding Obstacles and Exploring Space: “As cytoplasmic dynein often steps sidewise to adjacent proto-filaments, a bidirectional cargo could find itself on the opposite side of the microtubule even after a short minus-end excursion. If it now switches back to kinesin I, it can pass the obstacle. Bidirectionally moving cargoes should, therefore, be less likely to contribute to disastrous traffic jams …. The random walk of bidirectional cargoes allows a single cargo to explore a large region of cellular space, especially if tracks are disordered.”
- Error Correction: “During unidirectional transport, the critical event that determines directionality of motion is the attachment to either a plus- or minus-end motor. A wrong attachment will cause misdelivery of the cargo. During bidirectional transport, the net direction of transport is determined by the balance of plus- and minus-end trips and can, therefore, be continually evaluated and even altered if physiological conditions change. Thus, bidirectional transport may facilitate error correction.
It must be remembered that these motors are operating in the dark without eyes, like automated railroad cars. They don’t have sentient drivers on radios, but rather respond to chemical signals in the environment. Apparently these behaviors achieve the best solution to many complex problems. “Bidirectional transport by opposite-polarity microtubule motors is just one example of multiple motors working together to achieve carefully choreographed transport,” Welte says, as he concludes with a list of open problems needing further elucidation.
1Michael A. Welte, “Bidirectional Transport along Microtubules,” Current Biology, Volume 14, Issue 13, 13 July 2004, Pages R525-R537, http://dx.doi.org/10.1016/j.cub.2004.06.045.
Think of a 12-year-old kid on motorized rollerblades, one foot going forward, the other reverse. Imagine the tricks he could accomplish (with a little practice) switching from one foot to the other (or the bloody knees as he experiments the first time). Now make the wheels run on monorails. Imagine a complex tangle of rails, some blue, some red, going off in all directions, more dizzying than an amusement park roller coaster. The kid is supposed to put the left foot on the red rails and the right foot on the blue rails (one foot at a time, of course). Now hand him a package to deliver, and put a thousand other kids on the system going in all directions with packages of their own. The rails are also in constant motion, some growing and some shrinking. If the mental picture is becoming too complicated to dwell on further, just realize that something like this is happening in every cell of your body right now. This intracellular transport system is only a small part of a miniaturized city with many other vital tasks being performed flawlessly. The transportation system alone has a large infrastructure of support services. There are linemen for the monorails, pit crewmen for motor repair, traffic cops, construction crews, shippers, receivers and much more, without even considering what the cargoes are and what they do when they arrive.
The interior of a cell is a whirlwind of constant activity, all necessary just to sustain life. Rocks do not do this. Evolutionists may jawbone about these systems emerging from chance and natural selection over millions of years of purposeless motion, but the more we can exhibit the details of cellular perfection, the less plausible their story is going to seem to any rational observer. This system is crying out for visualization. The wonder of intracellular transport would come alive if magnified a million times.2