Researchers found that the size limit for entry is much greater than previously thought, allowing most of a cell's proteins into cilia. The researchers believe that the specific collection of proteins in each cilium, customized to the needs of each cell type, is determined by whether and how cilia keep proteins inside once they enter –– not which ones they allow in initially.
A cilium stands out in blue fluorescence against the yellow fluorescence of the rest of the cell.
Credit: Inoue lab
"According to our experiments, 90 percent of the proteins in mammalian cells should be able to fit inside cilia based on their size," says Takanari Inoue, Ph.D., assistant professor of cell biology at the Johns Hopkins University School of Medicine. "But most of them have never been found [inside the cilia], so we think that most proteins do wander in at some point, but only certain ones remain inside."
So-called "primary cilia" have been attracting intense attention as recent research has confirmed their role in monitoring the cell's exterior environment and conveying information to the rest of the cell using an arsenal of signals stored inside the thin interior of each antenna-like cilium. The results of this study, which help explain how that arsenal is developed, will be published online in the journal Nature Chemical Biology on May 12.
Primary cilia are found protruding from most cells in a wide variety of organisms, and defects in cilia have been implicated in everything from polycystic kidney disease to vision and hearing loss. In the kidney, they monitor the flow of urine; in the eye, they sense the wavelength of light; in cartilage, they sense pressure; and in the heart, blood flow. No matter where they are, Inoue says, their job is to translate such mechanical forces—or, in some cases, chemical ones—into molecular signals for the cell, so that it can respond appropriately to its environment.
The signaling molecules inside cilia are tailored to the required responses. For example, some are proteins that bind to DNA to modify gene activity, letting a cell respond to environmental cues by producing more of a particular protein.
The only way into the cilial column is through a hole at its base. "A cilium forms like a short drinking straw being pushed outwards from inside an inflated balloon," says Inoue. "What we don't know is whether there is some sort of cap over the hole, regulating what goes in and out. We found that more signaling molecules can enter the straw than we thought."
"Primary cilia are really difficult to study," Inoue says, "because they are so small and narrow, with each cilium just 1/10,000th the volume of the rest of the cell."
Previous research in other laboratories suggests that a fixed pore exists at the base of a cilium that only allows relatively small molecules inside. By developing more sensitive experimental methods, the Inoue group was able to show that molecules almost 10 times larger than those known before could enter.
Specifically, they first engineered an anchor-like molecule that selectively embedded itself in the membranes of cilia. On the inside end of the anchor was half of a "molecular snapper." Inside the watery interior of the cell, the team placed fluorescent molecules of known size, fitted with the other half of the molecular snapper. If these fluorescent molecules entered cilia, they would carry their fluorescence with them and be trapped inside when the snappers clicked together, allowing the researchers to easily take images of them.
By repeating this experiment many times with molecules of increasing size, the Inoue team was able to show that every molecular size they tested was able to enter the cilia. The only difference between the molecules of different sizes was their rate of entry: Smaller molecules entered more quickly than larger ones.
Figuring out how cilia select their captives is a question for another study, Inoue says.
Other authors of the report include Yu-Chun Lin, Benjamin Lin, Siew Cheng Phua, John Jiao and Andre Levchenko of the Johns Hopkins University School of Medicine; Pawel Niewiadomski and Rajat Rohatgi of the Stanford University School of Medicine; and Hideki Nakamura and Takafumi Inoue of Waseda University.
This work was supported by grants from the National Institute of General Medical Sciences (GM092930), the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK090868), the National Cancer Institute (R00CA129174), the National Institute of Neurological Disorders and Stroke (R21NS074091) and the Pew Foundation.
Link to article (after embargo lifts): http://dx.doi.org/10.1038/NChemBio.1252
Catherine Kolf | EurekAlert!
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Power and Electrical Engineering
16.01.2017 | Information Technology
16.01.2017 | Power and Electrical Engineering