Pair of proteins gets brain cells into shape

December 20, 2012, Helmholtz Association of German Research Centres

Scientists at the German Center for Neurodegenerative Diseases in Bonn have gained new insights into the early phase of the brain's development. In cooperation with researchers of the Max Planck Institute of Neurobiology, the University of Bonn and other German and international colleagues they identified two proteins that control the formation of cell protuberances. The typical ramifications through which nerve cells receive and forward signals ultimately originate from these outgrowths.

The study conducted by Prof. Frank Bradke's team provides indications on brain development and about the causes of diseases of the nervous system. The results have now been published in Neuron.

Under the microscope, the brain appears as a network of intricate beauty comprising billions of (the so-called "neurons") linked together. This network is engaged in a constant process of sharing information. The signals are transmitted from neuron to neuron through fine ramifications of the cell body. However, to acquire this typical structure, young nerve cells have first to go through a shape transformation. "Young neurons have a rather inconspicuous form. They tend to be round and are reminiscent of cherries," comments Frank Bradke, group leader at the DZNE in Bonn. "At this stage, the neuron is much like an island. It is insulated and does not have any direct contact with other cells."

Consequently, nerve cells have to go through a phase of change while they are still in the early stages of their development. To date, little was known about how the cells master this transformation, which is so important for their function. It is essential for the brain's development that its develop contacts to a multitude of other cells. The initial step of this process is that tiny extensions, the so-called "neurites" protrude out of the cell body. The study conducted by the researchers in Bonn and their colleagues sheds light on this process.

A dynamic duo gets its grip on the cell's corset

Investigating mouse , the neuroscientists were able to identify the three key players involved in the shape change: the cell's cytoskeleton, which consists of specific proteins that give the cell its form and stability, as well as the two proteins named "ADF" and "cofilin." "We were able to show that these two proteins do have a significant impact on cell structure," explains Dr. Kevin Flynn, a postdoc researcher in Bradke's team and first author of the report published in "Neuron". "Much like scissors they cut through the support corset of the cell in the proper location. Neurites can subsequently develop through these gaps."

For this to occur several processes have to work hand in hand: along its perimeter, the neuron receives its stability mainly through a network of actin filaments, string shaped molecules. The proteins ADF and cofilin can alter this structure by dissolving the actin filaments and enabling fragments resulting from this process to be carried away. As a result, other components of the cytoskeleton – the microtubules – are able to come to action. The microtubule migrate through the newly opened gap and form a new cell protuberance.

Impact on the development of the brain

In their study, the researchers demonstrated the significance of the two proteins in nerve cell development. In certain mice, the production of ADF and cofilin was virtually halted. As a result the brains of newborn animals had severe abnormalities. Analysis of their brain cells indicated that they had failed to develop any neurites.

"Our study shows that the proteins ADF and cofilin, and their interaction with actin filaments, are key factors for ," comments Bradke. However, the development of neurites is also of relevance in other contexts. For instance, nerve cells have to regrow their connections after an injury. In addition, a number of diseases and malformations of the nervous system are linked to underdeveloped neurites. "We now have a better understanding of the molecular processes that are involved in this important process."

Explore further: Cell research opens new avenues in combating neurodegenerative diseases

More information: "ADF/cofilin-mediated Actin Retrograde Flow Directs Neurite Formation in the Developing Brain," Kevin C. Flynn, Farida Hellal, Dorothee Neukirchen, Sonja Jacobs, Sabina Tahirovic, Sebastian Dupraz, Sina Stern, Boyan K. Garvalov, Christine Gurniak, Alisa Shaw, Liane Meyn, Roland Wedlich-Söldner, James R. Bamburg, J. Victor Small, Walter Witke, Frank Bradke, Neuron. www.cell.com/neuron/abstract/S … -6273%2812%2900897-5

Related Stories

Cell research opens new avenues in combating neurodegenerative diseases

July 20, 2012
Scientists at the University of Manchester have uncovered how the internal mechanisms in nerve cells wire the brain. The findings open up new avenues in the investigation of neurodegenerative diseases by analysing the cellular ...

Recommended for you

New neuron-like cells allow investigation into synthesis of vital cellular components

January 22, 2018
Neuron-like cells created from a readily available cell line have allowed researchers to investigate how the human brain makes a metabolic building block essential for the survival of all living organisms. A team led by researchers ...

Finding unravels nature of cognitive inflexibility in fragile X syndrome

January 22, 2018
Mice with the genetic defect that causes fragile X syndrome (FXS) learn and remember normally, but show an inability to learn new information that contradicts what they initially learned, shows a new study by a team of neuroscientists. ...

Epilepsy linked to brain volume and thickness differences

January 22, 2018
Epilepsy is associated with thickness and volume differences in the grey matter of several brain regions, according to new research led by UCL and the Keck School of Medicine of USC.

Research reveals atomic-level changes in ALS-linked protein

January 18, 2018
For the first time, researchers have described atom-by-atom changes in a family of proteins linked to amyotrophic lateral sclerosis (ALS), a group of brain disorders known as frontotemporal dementia and degenerative diseases ...

Fragile X finding shows normal neurons that interact poorly

January 18, 2018
Neurons in mice afflicted with the genetic defect that causes Fragile X syndrome (FXS) appear similar to those in healthy mice, but these neurons fail to interact normally, resulting in the long-known cognitive impairments, ...

How your brain remembers what you had for dinner last night

January 17, 2018
Confirming earlier computational models, researchers at University of California San Diego and UC San Diego School of Medicine, with colleagues in Arizona and Louisiana, report that episodic memories are encoded in the hippocampus ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.