Kinesin protein walking on microtubule

How Cell controls its traffic: insights into a molecular mystery

You are stuck in a traffic jam for an hour, exhausted and disgusted. Listening to music for a long time becomes seemingly boring. Suddenly your scientific mind triggers to ponder the question of whether is there any traffic system inside our body. Well, there must be. Otherwise, how molecules such as hormones, enzymes, and neurotransmitters are delivered to other places inside the cell or exported out of the cell. There exists an affluent traffic system inside a normal cell and mostly motor proteins build it up. Cytoskeleton composed of mainly actin and tubulin proteins constitutes the transport network which extends from nucleus to plasma membrane inside the cytosol. Some motor proteins are of Porter family, it carries molecular cargo from source to the destination using a particular track in a specific direction. Like kinesins move along microtubule from center of the cell to the periphery while dyneins use the same track to walk in the opposite direction. However, myosin V walks toward the periphery along the actin filament. They move exactly like a (wo) man walks. As for example, kinesin has two heads; while one head is bound to the microtubule other unbinds with the help of ATP and diffuses to step past the leading head. This process alternates between these heads, hence executing directed walk in ‘hand-over-hand’ fashion. This is all about how cellular trucks move on the highway in a busy city. Now comes the packaging and delivery part. Usually, the proteins that have to be delivered are too large to pass directly through the membrane. So they are wrapped up inside a tiny container of fatty membrane called vesicle. These vesicles are then attached to a specific porter (e.g.: kinesin) which hauls along the filament toward the target. Some vesicles have unusual ways to get into the target. They form actin protein at their rear, polymerization of which into short filament gives thrust to move them forward like a jet pack. When the vesicles are on target, a protein complex enables them to dock and fuse with the target membrane. The proteins in the cargo and those in the membrane bind each other like the two sides of a zipper.

Animated representation of a Kinesin protein walking on a micro tubule © Hoogenraad lab | Utrecht University

The fact that out of many proteins they bind only with those ones which have some specific combinations, ensures that delivery location is very much precise. This principle operates for importation as well as for exportation, outside or inside the cell. Professor James Rothman, of Yale University, discovered the protein complex causing fusion while he was studying vesicle transport in mammalian cell during the 1980s and 1990s. He was awarded 2013 Noble prize in physiology with two other scientists, Prof. Randy W. Schekman, of the University of California, Berkeley, and Dr. Thomas C. Südhof, of Stanford University. According to the press release, “In the 1970s Prof. Randy Schekman decided to study its genetic basis by using yeast as a model system. In a genetic screen, he identified yeast cells with defective transport machinery, giving rise to a situation resembling a poorly planned public transport system. Vesicles piled up in certain parts of the cell. He found that the cause of this congestion was genetic and went on to identify the mutated genes. Schekman identified three classes of genes that control different facets of the cell´s transport system… some of the genes Schekman had discovered in yeast coded for proteins corresponding to those Rothman identified in mammals, revealing an ancient evolutionary origin of the transport system.”

Kinesin-Walking © John Liebler

Now this brings us into a question: is the cargo delivered in the precise time?

Prof. Thomas Südhof, another awardee, has done the pioneering work to explain the question. Here is how press release described his work:

Thomas Südhof was interested in how nerve cells communicate with one another in the brain. The signaling molecules, neurotransmitters, are released from vesicles that fuse with the outer membrane of nerve cells by using the machinery discovered by Rothman and Schekman. But these vesicles are only allowed to release their contents when the nerve cell signals to its neighbors. Calcium ions were known to be involved in this process and in the 1990s, Südhof searched for calcium sensitive proteins in nerve cells. He identified molecular machinery that responds to an influx of calcium ions and directs neighbor proteins rapidly to bind vesicles to the outer membrane of the nerve cell. The zipper opens up and signal substances are released.  Südhof’s discovery explained how temporal precision is achieved and how vesicle’s contents can be released on command.”

Without such exquisitely planned organization, the cell would lapse into chaos like our city does. Any error in such finely tuned cellular transport leads to a variety of diseases including diabetes and a number of neurological (e.g.: Alzheimer’s disease) and immunological disorders. There are still some basic unanswerable questions to be solved like the exact mechanism of the diseases and the way they can be cured. Let’s hope, we shall get the answers in near future.

So, Be Curious. Be Healthy.

“Harvard University selected XVIVO to develop an animation that would take their cellular biology students on a journey through the microscopic world of a cell, illustrating mechanisms that allow a white blood cell to sense its surroundings and respond to an external stimulus.”


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The author is pursuing Ph.D. in the field of ‘Theoretical Chemistry’ from Indian Institute of Science (IISc), Bangalore, India.