Every day billions of cells die in our body and need to be replaced by newly dividing cells. Cell division is a beautifully orchestrated process that involves multiple critical steps. At the very end, “cellular abscission” splits the membrane and thereby gives birth to two daughter cells. Abscission is executed by a protein machinery named ESCRT-III.
ESCRT-III consists of many subunits that form spiral-shaped filaments to constrict the membrane tube connecting the daughter cells until it splits. Insights into the function of ESCRT-III are also interesting for many other biological processes – as this machinery also pinches off viruses from the host cell membrane, and seals holes in cellular and nuclear membranes.
Previous models proposed that ESCRT-III forms stable filaments that constrict membranes by changing their curvature. However, such static mechanism would be different from most other cellular filament systems, like microtubules or actin filaments, which continuously turn over subunits as they change their shape.
An international research team led by IMBA group leader Daniel Gerlich and Aurélien Roux from the University of Geneva set out to explore for the first time, whether ESCRT-III undergoes dynamic remodeling. To investigate this, the team applied cutting-edge microscopy to visualize the dynamics of ESCRT subunits live in human cells.
“We were very excited to find that ESCRT assemblies rapidly turn over their subunits, and that this is orchestrated by an enzyme called VPS4. We discovered that this dynamic turnover removes growth-inhibiting ESCRT-III subunits and thereby stimulates the addition of new subunits. This was surprising, because VPS4 was previously considered to mainly disassemble ESCRT-III filaments, but it actually promotes growth”, explains Beata Mierzwa, PhD student at the Vienna BioCenter and first author of the study.
To study the molecular details of ESCRT-III reorganization, the researchers recapitulated the process in a test tube using purified proteins. They then used high-speed atomic force microscopy to directly visualize dynamically growing and shrinking spiral-shaped filaments.
“Our findings provide a new model for how ESCRT-III might deform membrane tubes over large distances, which was difficult to imagine in light of the previous models of persistent filaments. This will be relevant for many other biological processes involving the ESCRT-III machinery.” states Daniel Gerlich.
"Dynamic instability in ESCRT-III assemblies”
Beata E. Mierzwa, Nicolas Chiaruttini, Lorena Redondo-Morata, Joachim Moser von Filseck, Julia König, Jorge Larios, Ina Poser, Thomas Müller-Reichert, Simon Scheuring, Aurélien Roux, Daniel W. Gerlich
Nature Cell Biology, DOI: 10.1038/ncb3559
IMBA - Institute of Molecular Biotechnology is one of the leading biomedical research institutes in Europe focusing on cutting-edge functional genomics and stem cell technologies. IMBA is located at the Vienna Biocenter, the vibrant cluster of universities, research institutes and biotech companies in Austria. IMBA is a subsidiary of the Austrian Academy of Sciences, the leading national sponsor of non-university academic research.www.imba.oeaw.ac.at
About the Vienna BioCenter
The Vienna BioCenter (VBC) is a leading life sciences location in Europe, offering an extraordinary combination of research, education and business on a single campus. About 1,600 employees, more than 1,000 students, 93 research groups, 16 biotech companies, and scientists from more than 40 nations create a highly dynamic environment. www.viennabiocenter.org
VBC PhD Programme
Much of the research leading to this publication was carried out by a PhD student of the VBC PhD Programme. Interested in doing a PhD that could be this successful? Then read more on the VBC PhD Programme webpage.
Mag. Ines Méhu-Blantar | idw - Informationsdienst Wissenschaft
Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides
16.07.2018 | Tokyo Institute of Technology
The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
16.07.2018 | Physics and Astronomy
16.07.2018 | Life Sciences
16.07.2018 | Earth Sciences