Brain researcher Hiroshi Kawabe has discovered the workings of a process that had been completely overlooked until now, and that allows nerve cells in the brain to grow and form complex networks. The study, which has now been published in the journal Neuron, shows that an enzyme which usually controls the destruction of protein components has an unexpected function in nerve cells: it controls the structure of the cytoskeleton and thus ensures that nerve cells can form the tree-like extensions that are necessary for signal transmission in the brain. (Neuron, February 11, 2010)
In the brain of mice, which cannot produce Nedd4-1, the extensions of nerve cells are shorter and of much simpler construction (example top) than in the brain of normal mice (example bottom). Image: Hiroshi Kawabe
In order to be able to receive signals from other cells, nerve cells form complex extensions called dendrites (from the Greek ‘dendron’ meaning tree). The growth of dendrites in the human brain takes place mainly during late embryonic and infantile brain development. During this phase, dendrites, with a total length of many hundred kilometres, grow from the 100 billion nerve cells in our brain. The result is a highly-complex network of nerve cells that controls all bodily functions - from breathing to complicated learning processes.
In order that this incredible growth phase of brain development does not lead to chaos, the growth of the dendrites must be accurately controlled. In fact, a large number of signal processes control the direction and the speed of dendrite growth by influencing the structure of the cytoskeleton, which is inside the growing dendrite and responsible for its shape and extension.
The Göttingen-based brain researcher Hiroshi Kawabe has now discovered exactly how the growth of the cytoskeleton is controlled during the dendrite development. Using specially bred genetically engineered mice, the Japanese guest scientist, who conducts research at the Max Planck Institute for Experimental Medicine, discovered that the Nedd4-1 enzyme is essential for regular dendrite growth. Nedd4-1 is an enzyme that usually controls the degradation of protein components in cells by combining them with another protein called ubiquitin. The cell identifies these ubiquitinated molecules as "waste" and degrades them. In some cases, however, the ubiquitination does not lead to the degradation of the marked protein but changes its function instead.
Nedd4-1 prevents degradation of the cytoskeleton
Hiroshi Kawabe has now shown that the Nedd4-1 enzyme ubiquitinates a signal protein called Rap2, and thus prevents it causing the dismemberment of the cytoskeleton and the collapse of the dendrites. "As long as Nedd4-1 is active, the nerve cell dendrites can grow normally," reports Kawabe. "In its absence, the dendrite growth comes to a standstill and previously formed dendrites collapse, with dramatic consequences for the function of nerve cell networks in the brain." There are, however, probably a number of parallel operating signal paths which control the dendrite growth. This explains why nerve cells can also form dendrites without Nedd4-1 - albeit significantly fewer in number and shorter. The Nedd4/Rap2/TNIK mechanism would then be only one of several that can partially compensate each other.
Kawabe's discovery provides important new insight into the mechanisms which control the development of the brain. "What is surprising is that no-one has investigated this before," says the Japanese biochemist. Scientists have long been aware that Nedd4-1 is one of the most prevalent ubiquitination enzymes in nerve cells and is produced with great frequency in the developmental phase when nerve cells grow and form their dendrites. As Kawabe points out, the function of Nedd4-1 has already been investigated in dozens of studies. "But very little work has been carried out on its role in nerve cell development, which would have been the obvious thing to do."
Original work:Kawabe, H., Neeb, A., Dimova, K., Young, S.M.Jr. Takeda, M., Katsurabayashi, S., Mitkovski, M., Malakhova, O.A., Zhang, D.-E., Umikawa, M., Kariya, K., Goebbels, S., Nave, K.-A., Rosenmund, C., Jahn, O., Rhee, J.-S. and Brose, N.
Neuron 65, 358-372 (2010)
Contact:Dr. Hiroshi Kawabe
Barbara Abrell | EurekAlert!
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy