Dyneins are tiny motors that walk along roadways called microtubules inside living cells. In yeast, they play a fundamental role in cell division-they pull the nuclear material in an oscillatory back-and-forth movement, tugging on the microtubules arising from it — a process critical for chromosome recombination. To do this, dynein needs to be tethered to the cell membrane via an anchor protein called Mcp5.
Researchers from the Indian Institute of Science (IISc) have now uncovered another key link in this chain- a lipid called PI(4,5)P2 that helps bind the anchor protein to the membrane. They also found that removing another type of motor protein called myosin‑I from the membrane affects dynein activity.
“When you deplete PI(4,5)P2 or delete myosin‑I, the effect is similar to when there is no anchor protein at all. Then dynein cannot stably attach to the membrane, pull on the microtubule, and the nucleus remains still,” says senior author Vaishnavi Ananthanarayanan, INSPIRE Faculty Fellow at the Centre for BioSystems Science and Engineering, IISc. Such cells either die or produce daughter cells with fewer spores.
Both myosin and dynein split ATP to power cell processes, but differ in shape, function and the pathways they traverse. “You don’t see many instances where one class of motor protein (myosin) actually modulates another class of motor protein (dynein),” says Ananthanarayanan.
The study, published in the Proceedings of the National Academy of Sciences, was carried out in a yeast variety called fission yeast.
Using a combination of genetics, microscopy and imaging, the researchers looked at how dynein organises itself and noticed that an equal number of dynein and anchor proteins cluster and connect at the membrane. “We then set out to find out how the anchor itself binds to the membrane because this is an important link for dynein activity,” says Ananthanarayanan. Building on previous research, they showed that a lipid called PI(4,5)P2 tethers the anchor protein to the membrane. PI(4,5)P2 was found to concentrate in sterol-rich areas of the membrane.
Ananthanarayanan then came across a paper suggesting that myosin‑I was responsible for maintaining similar sterol-rich regions in fission yeast. She and her team decided to test if removing myosin‑I had any effect on PI(4,5)P2 organisation and therefore on the cascade of events in the dynein pathway.
Interestingly, it did. Removing myosin‑I hampered PI(4,5)P2 clustering, which in turn affected anchor protein binding and dynein activity.
Figuring out dynein dynamics is important for understanding how cells divide both under normal circumstances and when division goes rogue, such as, in cancer, suggests Ananthanarayanan.
“The study also has implications for several other intracellular processes,” says Roop Mallik, Associate Professor, Department of Biological Sciences, Tata Institute of Fundamental Research, who was not involved with the research. In a developing brain, for example, nuclei of neurons must migrate over long distances. Mutations in a dynein-associated protein called Lis1 impair this motion and lead to a rare brain disorder called lissencephaly where the brain does not develop folds. “The migration of nuclei are again driven by dynein, with some similarity to nuclear oscillations in yeast,” he says.
Dyneins also ferry a wide variety of cargo inside mammalian cells. “By understanding one aspect of dynein function, we can speculate about what it does in other situations as well,” he says.
Ananthanarayanan’s lab is now looking at understanding how dynein juggles its roles in cargo transport and cell division, and what cues determine its activation inside cells.