Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Working the switches for axon branching

26.09.2018

Our brain is a complex network with innumerable connections between cells. Neuronal cells have long thin extensions, so-called axons, which are branched to increase the number of interactions. Researchers at the Max Planck Institute of Biochemistry (MPIB) have collaborated with researchers from Portugal and France to study cellular branching processes. They demonstrated a novel mechanism that induces branching of microtubules, an intracellular support system. The newly discovered dynamics of microtubules has a key role in neuronal development. The results were recently published in the journal Nature Cell Biology.

From the twigs of trees to railroad switches – our environment teems with rigid branched objects. These objects are so omnipresent in our lives, we barely notice them anymore. The branching can be achieved by different strategies. While railroad switches use special construction components, twigs grow from dormant buds in existent branches. However, not all biological branchings are so well understood.


In neuronal cells, the protein SSNA1 (pink) accumulates at branching sites in axons (top). The SSNA1 fibrils attach to the microtubules (green) and trigger branching (bottom).

© Naoko Mizuno, MPI of Biochemistry

How to branch an axon

Neuronal cells in the brain form complex networks in order to process information. These cells consist of a cell body with dendrites that collect incoming information and a single long axon that transmits information to other cells. Researchers from the group “Cellular and Membrane Trafficking” of Naoko Mizuno at the MPIB have studied the processes involved in branching of axons. The shape of the axon is stabilized by an internal support system of hollow tubes – the microtubules.

The microtubules are well-studied components of the cytoskeleton because they are involved in processes ranging from cell division and cell shape to intracellular transport. Hence, they combine diverse functions like intracellular railroad tracks with steel beams that maintain the architecture.

Microtubules are built in a directed manner from small tubulin protein building blocks that attach to the growing end of the microtubule. Tubulins align in parallel to each other and form a hollow tube. This hollow space gives rigidity to the microtubules.

“Researchers have not been able to observe branching of the microtubules”, says Nirakar Basnet, PhD student in Naoko Mizuno’s group and the first author of the study. “We show that a protein called SSNA1 accumulates at the sites where axons form branching points”, explains Basnet.

Let’s branch – but not too much

This observation cued the researchers to further study SSNA1. They found that the protein also forms filaments, albeit much thinner than the microtubules. These filaments attach to the surface of the growing microtubule and curve it outwards. The curvature forces branching of the growing microtubules.

It is a completely new principle of microtubule dynamics that the branching is inserted at the time of formation. Additionally, SSNA1 can cause branchings by connecting the ends of existing microtubules and by adding a new branch to an existing tubule, similar to the twig of a tree.

SSNA1 is indispensable for the neuronal development. Without SSNA1, the microtubules only form long unbranched tubes and consequentially the axons are also not branched. However, axon branching must be carefully regulated. When the researchers increased the concentration of the SSNA1 in cells, the microtubules increased in number but became shorter. “The local concentration of SSNA1 must be quite high to trigger branching”, states Basnet, “This could be a safety mechanism to prevent too much branching”.

Guiding the way for axon branching

Naoko Mizuno, group leader at the MPIB, describes SSNA1 as a “guide-rail” for the new branches of the microtubule. “The proteins form filaments that lead the way for the newly forming microtubule. In a way, SSNA1 is a railroad switch that leads to the branching of the track. But, unlike a railroad switch, it is not part of the track itself but rather marks the branching point from outside the track.” A railroad switch increases the number of destinations the train can reach. Similarly, the branched axons can make connections to a higher number of other neuronal cells.

Mizuno, explains that the current study was rendered possible by combining a range of microscopy technologies. “For example, we used cryoEM to study how SSNA1 attaches to the microtubules. With DNA-PAINT – a super-resolution light microscopy technology that was also developed at the MPIB – we could observe individual microtubules in the complex networks within the cells.” The synergy effect of combining different expertises from the Institute and from external partners contributed to the study which proposes a new concept in microtubule biology. “Many questions regarding cytoskeleton functions in other processes are still unanswered”, says Mizuno and speculates that the new branching mechanism could have implications in functions beyond axon branching. [CW]


About Naoko Mizuno
Naoko Mizuno studied biophysics at the University of Tokyo in Japan. In 2005, she received her PhD from the University of Texas Southwestern Medical Center in the USA. After her postdoctoral work, she became a research fellow at the the Laboratory of Structural Biology at the National Institutes of Health in the USA. Since 2013, Mizuno has been a group leader at the MPIB. She has received various awards and research grants, among them the EMBO Young Investigators award and an ERC consolidator grant.

About the Max Planck Institute of Biochemistry
The Max Planck Institute of Biochemistry (MPIB) belongs to the Max Planck Society, an independent, non-profit research organization dedicated to top-level basic research. As one of the largest Institutes of the Max Planck Society, about 800 employees from 45 nations work here in the field of life sciences. In currently about 35 departments and research groups, the scientists contribute to the newest findings in the areas of biochemistry, cell biology, structural biology, biophysics and molecular science. The MPIB in Munich-Martinsried is part of the local life-science-campus in close proximity to the Max Planck Institute of Neurobiology, a Helmholtz Center, the Gene-Center, several bio-medical faculties of the Ludwig-Maximilians-Universität München and the Innovation and Founding Center Biotechnology (IZB). http://biochem.mpg.de

Wissenschaftliche Ansprechpartner:

Naoko Mizuno, PhD
Cellular and Membrane Trafficking
Max Planck Institute of Biochemistry
Am Klopferspitz 18
82152 Martinsried/Munich
Germany
E-mail: mizuno@biochem.mpg.de
http://www.biochem.mpg.de/en/rg/mizuno

Originalpublikation:

N. Basnet, H. Nedozralova, A. Crevenna, S. Bodakuntla, T. Schlichthaerle, M. Taschner, G. Cardone, C. Janke, R. Jungmann, M. Magiera, C. Biertümpfel, N. Mizuno: Microtubule nucleation factor SSNA1 induces direct branched microtubules; its implications in axon branching. Nature Cell Biology, September 2018
DOI: 10.1038/s41556-018-0199-8

Dr. Christiane Menzfeld | Max-Planck-Institut für Biochemie

Further reports about: Biochemie MPIB Max-Planck-Institut axons filaments microtubule microtubules railroad

More articles from Life Sciences:

nachricht Nanocages in the lab and in the computer: how DNA-based dendrimers transport nanoparticles
19.10.2018 | University of Vienna

nachricht Less animal experiments on the horizon: Multi-organ chip awarded
19.10.2018 | Fraunhofer-Institut für Werkstoff- und Strahltechnik IWS

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Goodbye, silicon? On the way to new electronic materials with metal-organic networks

Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz (Germany) together with scientists from Dresden, Leipzig, Sofia (Bulgaria) and Madrid (Spain) have now developed and characterized a novel, metal-organic material which displays electrical properties mimicking those of highly crystalline silicon. The material which can easily be fabricated at room temperature could serve as a replacement for expensive conventional inorganic materials used in optoelectronics.

Silicon, a so called semiconductor, is currently widely employed for the development of components such as solar cells, LEDs or computer chips. High purity...

Im Focus: Storage & Transport of highly volatile Gases made safer & cheaper by the use of “Kinetic Trapping"

Augsburg chemists present a new technology for compressing, storing and transporting highly volatile gases in porous frameworks/New prospects for gas-powered vehicles

Storage of highly volatile gases has always been a major technological challenge, not least for use in the automotive sector, for, for example, methane or...

Im Focus: Disrupting crystalline order to restore superfluidity

When we put water in a freezer, water molecules crystallize and form ice. This change from one phase of matter to another is called a phase transition. While this transition, and countless others that occur in nature, typically takes place at the same fixed conditions, such as the freezing point, one can ask how it can be influenced in a controlled way.

We are all familiar with such control of the freezing transition, as it is an essential ingredient in the art of making a sorbet or a slushy. To make a cold...

Im Focus: Micro energy harvesters for the Internet of Things

Fraunhofer IWS Dresden scientists print electronic layers with polymer ink

Thin organic layers provide machines and equipment with new functions. They enable, for example, tiny energy recuperators. In future, these will be installed...

Im Focus: Dynamik einzelner Proteine

Neue Messmethode erlaubt es Forschenden, die Bewegung von Molekülen lange und genau zu verfolgen

Das Zusammenspiel aus Struktur und Dynamik bestimmt die Funktion von Proteinen, den molekularen Werkzeugen der Zelle. Durch Fortschritte in der...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Conference to pave the way for new therapies

17.10.2018 | Event News

Berlin5GWeek: Private industrial networks and temporary 5G connectivity islands

16.10.2018 | Event News

5th International Conference on Cellular Materials (CellMAT), Scientific Programme online

02.10.2018 | Event News

 
Latest News

Nanocages in the lab and in the computer: how DNA-based dendrimers transport nanoparticles

19.10.2018 | Life Sciences

Thin films from Braunschweig on the way to Mercury

19.10.2018 | Physics and Astronomy

App-App-Hooray! - Innovative Kits for AR Applications

19.10.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>