Coin tossing explains the activity of opposing molecular motors that transport cargo inside a cell


11 May 2018

Coin tossing explains the activity of opposing molecular motors that transport cargo inside a cell

 

By Dr. Paulomi Sanghavi, Early Career Fellow

Corresponding author-  Prof. Roop Mallik, Senior Fellow

Tata Institute of Fundamental Research (TIFR), Mumbai

Microtubules are hollow tubes made up of proteins that are part of the cell's overall skeleton and are responsible for maintaining the cell shape, transporting material inside the cell and cell division. Microtubules are used by eukaryotic cells to segregate their chromosomes during cell division. Microtubule motors Kinesin and Dynein are required for localization of many different organelles inside the cell. Most Kinesins transport cargoes towards microtubule plus-ends towards cell periphery while Dynein is a minus-end motor, which transports molecules towards cell center. How opposite polarity motors present on a cargo work together to achieve bidirectional transport is hotly debated. Some reports suggest that opposite motors are engaged in a Tug-of-War scenario where both motors pull against each other.  Thus, the direction of motion is dictated by the winning motor. On the contrary, another model proposes that motor activity is highly coordinated and only one motor is kept active at one given time.

In this study, we addressed how back and forth motion of early phagosomes is achieved by Kinesin and Dynein motors. Interestingly, we find that activity of Kinesin and Dynein motors on early phagosome is stochastic. Unlike the proposed models, we showed that inactivating one set of motors does not affect the activity of the opposite motor suggesting that both Kinesin and Dynein function independently of each other. Using mathematical modeling, we also showed that the choice between Kinesin and Dynein could be explained by tossing a hypothetical fair coin. Thus our model provides a conceptual framework for understanding bidirectional transport. We believe that the choice between Kinesin and Dynein motors can be affected by regulatory proteins or lipids or other molecules, which bias the coin hence allowing one motor to predominate and drive cargo transport to their respective sub-cellular sites.

Reference

Coin Tossing Explains the Activity of Opposing Microtubule Motors on Phagosomes. Paulomi Sanghavi, Ashwin D’Souza, Ashim Rai, Arpan Rai, Ranjith Padinhatheeri, Roop Mallik. Current Biology. April 2018

Banner image credit: Roop Mallik