Microtubules help to regulate cell structure throughout our bodies. A group of Japanese researchers have used cryo-electron microscopy to shed light on how a certain protein keeps microtubules stable, and regulates microtubule-based transport within cells. The new insights could help to develop medical treatment for diseases such as dementia and heart failure. These findings were published on October 1 in the online edition of the Journal of Cell Biology.
The research team was led by Professor Ryo Nitta and Project Professor Tsuyoshi Imasaki (Kobe University Graduate School of Medicine) in collaboration with team leader Mikako Shirouzu and Researcher Hideki Shigematsu (RIKEN), and Associate Professor Kiyotaka Tokuraku (Muroran Institute of Technology).
Cells in our bodies take on specialized shapes in order to function as part of organs and tissue. For example, nerve cells keep the brain and body closely linked by making a communications network between cell projections. Heart cells form lines of cylinders for effective muscle contraction.
To create these shapes, a framework of complex proteins make the cell "skeletons". The widest of these are known as microtubules, and their placement is regulated by microtubule-associated proteins.
Tau and MAP4 (both part of the Tau family) are "classic" microtubule-associated proteins. Tau is found in nerve cells, while MAP4 is expressed widely throughout our bodies such as the heart or skeletal muscle.
Excessive expression of these classic microtubule-associated proteins has been linked to Alzheimer's disease and heart failure. It can block the movement of motor protein kinesin, which uses microtubules as "rails" to transport various substances within cells.
The research team reconstructed the complex structure of microtubules, MAP4 and motor protein kinesin under laboratory conditions, and used cryo-electron microscopy to visualize the detailed three-dimensional structure (figure 1).
Their analysis revealed that MAP4 attaches to the long axes of microtubules and stabilizes them. The bonds between MAP4 and microtubules are located at two types of sites: for strong and weak interactions. At the weak sites, kinesin competes with MAP4 to bind with microtubules (see figure 2). If there is sufficient kinesin, it can displace the MAP4 at the weak sites and bind with the microtubules.
This leads to both MAP4 (at the strong anchor sites) and kinesin (at the weak sites) binding with microtubules at the same time. The team found that, as well as binding directly with microtubules, MAP4 also folds and accumulates above the microtubules.
The MAP4 in this area interacts with and secures kinesin, blocking the movement of kinesin above the microtubules. This shows how MAP4 stabilizes microtubules, and how it also blocks the transport functions of kinesin.
This research provides important information that could potentially help to create a new treatment strategy for cardiac hypertrophy and heart failure caused by overexpression of MAP4. It is also highly possible that Tau, which has an amino-acid sequence very similar to MAP4, could present the same structure. In this case, this study would also shed light on neurodegenerative diseases such as dementia.
Professor Nitta comments: "By revealing the micromorphology of the MAP4 and microtubule complex in cells, we hope this research will provide insights on a cellular level that can help us to combat diseases caused by cell change such as heart failure and dementia."
Eleanor Wyllie | EurekAlert!
Genetic differences between strains of Epstein-Barr virus can alter its activity
18.07.2019 | University of Sussex
Machine learning platform guides pancreatic cyst management in patients
18.07.2019 | American Association for the Advancement of Science
Adjusting the thermal conductivity of materials is one of the challenges nanoscience is currently facing. Together with colleagues from the Netherlands and Spain, researchers from the University of Basel have shown that the atomic vibrations that determine heat generation in nanowires can be controlled through the arrangement of atoms alone. The scientists will publish the results shortly in the journal Nano Letters.
In the electronics and computer industry, components are becoming ever smaller and more powerful. However, there are problems with the heat generation. It is...
Scientists have visualised the electronic structure in a microelectronic device for the first time, opening up opportunities for finely-tuned high performance electronic devices.
Physicists from the University of Warwick and the University of Washington have developed a technique to measure the energy and momentum of electrons in...
Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.
Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...
For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.
Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...
An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".
The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...
24.06.2019 | Event News
29.04.2019 | Event News
17.04.2019 | Event News
22.07.2019 | Physics and Astronomy
22.07.2019 | Life Sciences
22.07.2019 | Earth Sciences