Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Keeping our cells stable: A closer look at microtubules

01.10.2018

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).


Figure 1: A cryo-EM reconstruction of the microtubule-MAP4-kinesin complex.

Credit: Kobe University


Figure 2: Detailed structure of the microtubule-MAP4-kinesin complex (upper part) and structural model (lower part). See main text for details.

Credit: Kobe University

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!

More articles from Health and Medicine:

nachricht Inselspital: Fewer CT scans needed after cerebral bleeding
20.03.2019 | Universitätsspital Bern

nachricht Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

Im Focus: Revealing the secret of the vacuum for the first time

New research group at the University of Jena combines theory and experiment to demonstrate for the first time certain physical processes in a quantum vacuum

For most people, a vacuum is an empty space. Quantum physics, on the other hand, assumes that even in this lowest-energy state, particles and antiparticles...

Im Focus: Sussex scientists one step closer to a clock that could replace GPS and Galileo

Physicists in the EPic Lab at University of Sussex make crucial development in global race to develop a portable atomic clock

Scientists in the Emergent Photonics Lab (EPic Lab) at the University of Sussex have made a breakthrough to a crucial element of an atomic clock - devices...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Molecular motors run in unison in a metal-organic framework

20.03.2019 | Life Sciences

Active substance from plant slows down aggressive eye cancer

20.03.2019 | Life Sciences

Novel sensor system improves reliability of high-temperature humidity measurements

20.03.2019 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>