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The Cell’s Postal System

The manufacturing system of cells is elegantly designed to produce proteins and other complex molecules, which must then get to the right locations. Small cells like bacteria can probably do it by diffusion, but larger eukaryotic cells need a directed delivery system. As a result, eukaryotes have efficient motors to carry cargo, and a “postal system” to direct the motors to the appropriate destinations.

Destinations differ. Some cargos go to the growing front end of a migrating cell. Others must travel the length of a neuron’s long axon to get to their destination. And some have to be exported outside the cell. As an example, epithelial cells have three distinct surfaces, top, bottom, and sides. Each surface needs a different set of molecules delivered to it. Without this differentiation, tissues and organs made of epithelial sheets could not form or function properly,

In embryos, special “determinants,” either protein or RNA, have to be delivered to the right location in the developing egg or embryo. Once again, without these determinants the body plan of the nascent embryo is disturbed.

How is all this coordinated? How does the cell know where to deliver its products? What is the address system? Where precisely is the map that matches all these addresses? And who is the postman that matches address to map and delivers the package to the right address?

There are three “postmen,” dynein, kinesin, and myosin. For delivery to the periphery of the cell, the job is usually done by kinesin.

Kinesin is composed of two parts — two heavy chains that form the walking two-headed motor and its long coiled stalk, and two light chains, that bind at the end of the stalk and make a fan-like tail.

kinesin1.jpg

Illustration credit: Vladamir Shirinsky.

It has long been thought that the light chains are involved in binding to and perhaps distinguishing among the many cargos that kinesin delivers. It is also thought they play a regulatory role for the motor domain. If the kinesin heavy chains have no attached light chain, they fold on themselves and inactivate the motor. So the light chains function like an on-off switch for the motor, which helps to conserve energy. They may also serve to promote interaction and cooperation between dynein and kinesin.

There are multiple versions of the light and heavy chains. Some are generalists, and some are specific to particular cell types. We now know that defects in different kinds of heavy and light chains are associated with particular diseases, most notably Alzheimer’s.

What we do not know is how everything gets sorted to the right destination. There is much more work to be done, but progress is being made in determining some of the linking “address” proteins that bind the light chains.

This system is present in most if not all eukaryotes. In fact, it appears to date back to the first eukaryotes. Let’s consider how this system might have come about. All parts are necessary for it to work. To return to our metaphor, if the postman just started transporting things at random, what benefit would that be? Yet address molecules are of no use without a postman, or without paths to travel on. Thus directed transport requires a complicated set of interacting parts, each of which is essential.

Without these motors and their interacting proteins, migrating cells wouldn’t have the materials they need to move forward. Axons would die from lack of mitochondria and/or they would send signals very inefficiently. Epithelial cells would have their bottoms and tops confused. And embryos? A mess. 

Oh, and I haven’t mentioned that both kinesin and dynein are essential for chromosome movement and spindle formation during cell division.

 Amazing. Hard to sort out how it happened, isn’t it?

Photo source: Matthew Bednarick/Flickr.

Ann Gauger

Senior Fellow, Center for Science and Culture
Dr. Ann Gauger is Director of Science Communication and a Senior Fellow at the Discovery Institute Center for Science and Culture, and Senior Research Scientist at the Biologic Institute in Seattle, Washington. She received her Bachelor's degree from MIT and her Ph.D. from the University of Washington Department of Zoology. She held a postdoctoral fellowship at Harvard University, where her work was on the molecular motor kinesin.

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