How nerve cells grow

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How nerve cells grow

http://www.mpg.de/english/illustrationsDocumentation/documentation/pressReleases\

/2010/pressRelease20100219/

Göttingen-based Max Planck researcher decodes a molecular process that controls

the growth of nerve cells

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 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.

Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development

in cortical neurons.

Neuron 65, 358-372 (2010)