The transport routes of nutrients and messenger cargos can be compared to the traffic system of a city: A worldwide unique quantitative study of cell biologists of the University of Zurich shows that cells regulate the main routes, side routes and intersections by an intricate traffic control system, which guides the spatial and temporal distribution of substances within the cell.
Cells must transport nutrients and messenger cargos through its membrane and transport them within the cell at the correct time and place. This procedure is complex and is regulated with the help of specific genes. If disturbances in the transport mechanism arise, severe diseases, such as diabetes, cancer and diverse neurological pathologies, are the consequence.
The discovery of the molecular principles of cellular transport was honored with the Nobel Prize of physiology and medicine in 2013. While knowing the intracellular roads and the functioning of the cars that use these roads is essential knowledge, one cannot understand much of how a cell functions without knowing how all this traffic is regulated and controlled.
Cell and systems biologists of the University of Zurich could now create a first global map of the regulatory control systems of the majority of transport routes in a cell. This unique map has been published by the renowned scientific journal Cell as its cover story.
How cells uptake and transport cargos
Cells regulate the uptake of nutrients and messenger cargos and their transport within the cell. This process is known as endocytosis and membrane traffic. Different cargos dock onto substrate specific receptors on the cell membrane. Special proteins such as kinases, GTPases and coats, activate specific entry routes and trigger the uptake of the receptors into the cell. For their uptake, the receptors and docked cargos become enclosed by the cell membrane. In the next steps, the membrane invaginates and becomes constricted. The resulting vesicle is guided via several distinct stations, cellular organelles, to its final destination in the cell.
Cells regulate the main routes, side routes and intersections
For her study, Dr. Prisca Liberali, senior scientist in the team of Professor Lucas Pelkmans, sequentially switched off 1200 human genes. Using automated high-throughput light microscopy and computer vision, she could monitor and compare 13 distinct transport paths involving distinct receptors and cellular organelles. Precise quantifications of thousands of single cells identified the genes required for the different transport routes. Surprisingly, sets of transport routes are co-regulated and coordinated in specific ways by different programs of regulatory control.
Subsequently, Dr. Liberali calculated the hierarchical order within the genetic network and thereby identified the regulatory topology of cellular transport. “The transport into the cell and within the cells proceeds analogously to the cargo transport within a city” describes the scientist. “Like in a city, the traffic on the routes within a cell and their intersections is tightly regulated by traffic lights and signs to guide the cargo flow.”
Thanks to this unique quantitative map, the fine regulatory details of transport paths and processes within a cells could be mapped for the first time. Particularly the genes that encode for these traffic lights and switches are often de-regulated in disease. With this map, it is now possible to predict how this leads to traffic jams in the cells, causing the disease phenotype. Alternatively, since many drugs have been developed to target these traffic lights and switches, the map can be used to come up with possible drug combinations to target unwanted traffic, such as viruses, to the waste disposal system of the cell.
Prisca Liberali, Berend Snijder, Lucas Pelkmans. A hierarchical map of regulatory genetic interactions in membrane trafficking. Cell. June 5, 2014. DOI: http://dx.doi.org/10.1016/j.cell.2014.04.029
Dr. Prisca Liberali
Institut für Molekulare Biologie
Tel. +41 44 635 31 94 / +41 77 459 57 53
Tel. +41 44 634 44 39
Bettina Jakob | Universität Zürich
Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg
Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
19.10.2017 | Materials Sciences
19.10.2017 | Materials Sciences
19.10.2017 | Physics and Astronomy