They are tiny and hairy and sit on almost all of our cells. Of course we are talking about cilia, protein structures that are key to numerous functions of our body.
If their assembly is incorrect or incomplete, patients are unable to hear and their kidneys would lose the ability to filtrate blood. Scientists at the Max Planck Institute of Biochemistry in Munich-Martinsried have now been able to elucidate a fundamental mechanism mediating the transport of new building blocks to the cilia.
“The mechanism we investigated can explain how the cell provides new material for the cilia and how failures in this process lead to diseases like deafness“, says André Mourão, first author of the study.
Cilia are tiny hair-like protein structures, which reside on the surface of almost all cells of both humans and animals. They carry out a number of important tasks, like the transmission of acoustic signals within the ear, optical signal in our eyes and the movement of sperm cells.
This indicates how important these structures are. However, it also emphasizes how diseases which affect the cilia can severely impair the life of the respective patients. Bardet-Biedl Syndrome (BBS) is one such disease, in which affected individuals suffer from blindness and/or deafness, kidney failure and obesity.
Until now, researchers were able to find out that BBS is caused by alterations of a certain group of nineteen proteins (BBS1-19). In healthy cells these proteins constitute a molecular shuttle that transports new building blocks towards the cilia – the so-called BBSome.
In case the shuttle service does not work properly, the function of cilia is severely impaired. Researchers in the team of Esben Lorentzen at the MPI of Biochemistry recently identified the mechanism underlying the transport of the protein cargo in detail.
In the present study the scientists showed that the interaction of two particular proteins is necessary to deliver new building blocks to the cilia: Once the BBSome shuttle has uptaken its cargo, the molecule ARL6 is further needed to direct it to the cell surface where the cilia are located.
ARL6 docks to a certain part of the BBSome, the protein BBS1, making sure that the shuttle is carried towards its correct destination. According to the researchers this mechanism is conserved from humans to green algae. This is usually good evidence, that a feature is essential for survival.
A molecular shuttle gone astray
Esben Lorentzen gives an example, how crucial this mechanism is for our health: “Interestingly, 30 percent of all BBS patients have a mutation at a certain position of BBS1, the consquences of which were not fully understood before. We were now able to show, that this mutation affects the binding between ARL6 and BBS1, inhibiting the interaction of those two molecules.”
The scientists assume that this prevents the protein shuttle from being directed to its correct destination, subsequently leading to a lack of protein supply in the cilia and a loss of their function. In the future, the scientists hope to clarify whether other proteins are involved in the process and which potential roles they might play.
A. Mourão, A.R. Nager, M.V. Nachury and E. Lorentzen: Structural basis for membrane targeting of the BBSome by ARL6. NSMB, November 17, 2014.
Dr. Esben Lorentzen
Max Planck Institute of Biochemistry
Am Klopferspitz 18
Max Planck Institute of Biochemistry
Am Klopferspitz 18
Tel. +49 89 8578-2824
Anja Konschak | Max-Planck-Institut für Biochemie
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy