Technische Universität München
How to start a nanomotor? Research team reconstructs motor-cargo complex for ciliary transport
TECHNICAL UNIVERSITY OF MUNICH
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How to start a nanomotor?
Research team reconstructs motor-cargo complex for ciliary transport
Most people have never heard of them, and yet every living being needs them to survive: fine protrusions of cells known as cilia. They allow sperm to move, form fine protective hairs in the lungs and play a crucial role in the differentiation of organs in embryos. A research team at the Technical University of Munich (TUM) has now reconstructed the protein complex responsible for transport within cilia, which plays a decisive role in their functioning.
Flagellates need them to move, roundworms to find food, and sperm to move towards the egg: cilia. These excrescences of eukaryotic cells even ensure that the human heart ends up in the right place - cilia control the organ development of the growing fetus. "This Multifunctionality is absolutely fascinating," says Dr. Zeynep Ökten, biophysicist in the Physics Department of the Technical University of Munich.
Only in recent years the significance of cilia for signal transduction has been recognized. "To date, we know very little about which biochemical processes control the various functions. This makes understanding the basic mechanisms even more important," emphasizes the scientist.
Green dots in the focus
The scientist holds a glass plate with thin, liquid-filled capillaries up to the light. There is not much to see - merely a clear and transparent liquid. Only under a fluorescence microscope does the movement of compounds marked with dye become visible: green dots, all striving in one direction.
As if on a highway, the transport proteins migrate along the thin channels of the cilia. But just how these engines are started up, remained a mystery until now. That is why Zeynep Ökten and her team decided to reconstruct the protein complex.
Bottom-up instead of top-down
The building blocks of the protein complex stem from the model organism of the Caenorhabditis elegans nematode. It uses its cilia to find food and detect hazards. The biologists have already identified dozens of proteins that affect the function of nematode cilia.
"Here, the classical top-down approach reaches its limits because too many building blocks are involved," explains Ökten. "To understand the intra-flagellar transport, IFT for short, we thus took the opposite approach, studying individual proteins and their interactions from the bottom up."
The needle in a protein haystack
The work resembled the proverbial search for the needle in a haystack. A variety of molecular compounds came into question. After months of experimentation, the researchers stumbled upon a minimal combination of four proteins. As soon as these proteins fuse into a complex, they begin migrating through the capillaries of the sample carrier.
"When we saw the images of the fluorescence microscope, we immediately knew: Now we have found the parts of the puzzle that start the engine," recalls Ökten. "If just one of these components is missing, due to a genetic defect, for example, the machinery will fail - which, because of the cilia's importance, is reflected in a long list of serious diseases."
Publication:
Mohamed A. A. Mohamed, Willi L. Stepp and Zeynep Ökten
Reconstitution reveals motor activation for intraflagellar transport
Nature, vol. 557, p 387-391 (2018) - DOI: 10.1038/s41586-018-0105-3
https://www.nature.com/articles/s41586-018-0105-3
Further information:
The work was funded by the European Research Council and the German Research Foundation (DFG) as part of the Cluster of Excellence Munich Center for Integrated Protein Science (CIPSM).
High-resolution images and video:
https://mediatum.ub.tum.de/1447270
Contact:
Dr. Zeynep Ökten
Department of Physics, E22
Technical University of Munich
James-Franck-Str. 1, 85748 Garching
Tel.: +49 89 289 12885 - E-Mail: zoekten@ph.tum.de
Web: http://bio.ph.tum.de/home/dr-oekten/oekten-home.html
Technical University of Munich (TUM) is one of Europe's leading research universities, with about 550 professors, around 10,000 academic and non-academic staff, and 41,000 students. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, combined with economic and social sciences. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with a campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006 and 2012 it won recognition as a German "Excellence University." In international rankings, TUM regularly places among the best universities in Germany. www.tum.de