Pair of Proteins Gets Brain Cells into Shape

Photo: Nerve cells

Wild-type (left) and ADF/Cofilin Knockout
Neurons (right) isolated from the cortex
and cultured for 2 days with the actin
(green) and microtubule (red) cytoskeletons
labeled; © K. Flynn

The study conducted by Professor Frank Bradke’s team provides indications on brain development and about the causes of diseases of the nervous system. The study was in cooperation with researchers of the Max Planck Institute of Neurobiology, the University of Bonn and other German and international colleagues.

Under the microscope, the brain appears as a network of intricate beauty comprising billions of nerve cells (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 Bradke. “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 neurons 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 sheds light on this process.

Investigating mouse brain cells, 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 Doctor Kevin Flynn. “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 protein 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.

MEDICA.de; Source: German Center for Neurodegenerative Diseases (DZNE)