Common

The way neurons grow

The Göttingen Neuroscientist Hiroshi Kawabe has cleared up a process entirely overseen so far, which enables neurons in the brain to grow and form complex networks. The study now published in the Neuron journal demonstrates that a certain enzyme that should be regulating the deconstruction of protein units, in fact has an entirely unexpected function: it directs the construction of the cytoskeleton and thereby ensures that the neurons are able to grow axons required for signal conduction in the brain. (Neuron, February 11th 2010)

In order to receive signals from other cells, neurons develop complicated extensions, called Dendrites like the Greek word for tree, “Dendron”. Dendrite growth in the brain occurs primarily in the late embryonic stage and in early childhood development of the brain. During this phase dendrites with a cumulative length of several hundred kilometres grow from the more than 100 billion neurons in our brain. The result is a highly complex network of neurons regulating all bodily functions - including breathing or complicated learning processes.

In order for this tremendously fast growth phase to not end in chaos, the growth has to be strictly controlled. In fact, numerous signal processes steer the direction and pace of dendrite growth by influencing the erection of the cytoskeleton, which is responsible for the shape and elongation within the growing out dendrite.

How exactly the process of growth of the cytoskeleton is regulated during dendrite development has now been figured out by the Göttingen brain scientist Hiroshi Kawabe. The Japanese visiting researcher working at the Max-Planck Institute for experimental medicine has discovered that the enzyme Nedd4-1 is indispensable for normal dendrite growth within specifically bred and genetically altered mice.
Nedd4-1 is an enzyme that generally regulates the degeneration of protein units within cells by connecting it to another protein called Ubiquitin. The ubiquitinated molecules are recognized as “waste” by the cell and subsequently degenerated. In some cases however, the ubiquitination does not cause degeneration but alters its functionality.

Nedd4-1 obstructs cytoskeleton’s degeneration

Hiroshi Kawabe verified that the enzyme Nedd4-1 ubiqutinates a signal protein called Rap2 and thereby keeps it from initiating the cytoskeletons fragmentation and the dendrites’ breakdown. “For as long Nedd4-1 is active, neural dendrites can grow normally”, says Kawabe. “In case it fails, the dendrite growth ceases and once formed dendrites collapse, having dramatic consequences for the neurons functionality in the brain.“ However, there probably is a number of parallely operating signal paths regulating the dendrite growth. Thus can be explained why neurons are able to build dendrites even without Nedd4-1, though those are much shorter and fewer in number. The Nedd4-1/Rap2/TNIK mechanism would then be just one of several mechanisms capable of partially compensating each other.

Kawabe’s discovery provides an important insight into the mechanisms of brain development. “Actually, it is surprising that no one has yet explored this“, the Japanese biochemist thinks. It has been known for a long time, that Nedd4-1 is one of the most common ubiqutination enzymes and is produced particularly often during the developmental stage where neurons grow and form their dendrites. Kawabe states that the Nedd4-1’s function has been investigated in dozens of studies so far. “However, there are no papers about its role within neurons, although this would seem quite obvious.

Orignal Publication:
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.
Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development in cortical neurons.
Neuron 65, 358-372 (2010)

For further information, please contact:
Dr. Hiroshi Kawabe
Max-Planck-Institut für Experimentelle Medizin
Göttingen
Phone: +49 551 3899 720
E-Mail: kawabe@em.mpg.de

Source: Quelle: Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

Thema: Biotechnology, Health and Medicine

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	Common The way neurons grow The Göttingen Neuroscientist Hiroshi Kawabe has cleared up a process entirely overseen so far, which enables neurons in the brain to grow and form complex networks. The study now published in the Neuron journal demonstrates that a certain enzyme that should be regulating the deconstruction of protein units, in fact has an entirely unexpected function: it directs the construction of the cytoskeleton and thereby ensures that the neurons are able to grow axons required for signal conduction in the brain. (Neuron, February 11th 2010) In order to receive signals from other cells, neurons develop complicated extensions, called Dendrites like the Greek word for tree, “Dendron”. Dendrite growth in the brain occurs primarily in the late embryonic stage and in early childhood development of the brain. During this phase dendrites with a cumulative length of several hundred kilometres grow from the more than 100 billion neurons in our brain. The result is a highly complex network of neurons regulating all bodily functions - including breathing or complicated learning processes. In order for this tremendously fast growth phase to not end in chaos, the growth has to be strictly controlled. In fact, numerous signal processes steer the direction and pace of dendrite growth by influencing the erection of the cytoskeleton, which is responsible for the shape and elongation within the growing out dendrite. How exactly the process of growth of the cytoskeleton is regulated during dendrite development has now been figured out by the Göttingen brain scientist Hiroshi Kawabe. The Japanese visiting researcher working at the Max-Planck Institute for experimental medicine has discovered that the enzyme Nedd4-1 is indispensable for normal dendrite growth within specifically bred and genetically altered mice. Nedd4-1 is an enzyme that generally regulates the degeneration of protein units within cells by connecting it to another protein called Ubiquitin. The ubiquitinated molecules are recognized as “waste” by the cell and subsequently degenerated. In some cases however, the ubiquitination does not cause degeneration but alters its functionality. Nedd4-1 obstructs cytoskeleton’s degeneration Hiroshi Kawabe verified that the enzyme Nedd4-1 ubiqutinates a signal protein called Rap2 and thereby keeps it from initiating the cytoskeletons fragmentation and the dendrites’ breakdown. “For as long Nedd4-1 is active, neural dendrites can grow normally”, says Kawabe. “In case it fails, the dendrite growth ceases and once formed dendrites collapse, having dramatic consequences for the neurons functionality in the brain.“ However, there probably is a number of parallely operating signal paths regulating the dendrite growth. Thus can be explained why neurons are able to build dendrites even without Nedd4-1, though those are much shorter and fewer in number. The Nedd4-1/Rap2/TNIK mechanism would then be just one of several mechanisms capable of partially compensating each other. Kawabe’s discovery provides an important insight into the mechanisms of brain development. “Actually, it is surprising that no one has yet explored this“, the Japanese biochemist thinks. It has been known for a long time, that Nedd4-1 is one of the most common ubiqutination enzymes and is produced particularly often during the developmental stage where neurons grow and form their dendrites. Kawabe states that the Nedd4-1’s function has been investigated in dozens of studies so far. “However, there are no papers about its role within neurons, although this would seem quite obvious. Orignal Publication: 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. Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development in cortical neurons. Neuron 65, 358-372 (2010) For further information, please contact: Dr. Hiroshi Kawabe Max-Planck-Institut für Experimentelle Medizin Göttingen Phone: +49 551 3899 720 E-Mail: kawabe@em.mpg.de Source: Quelle: Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Thema: Biotechnology, Health and Medicine	Drucken Zurück