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.”