Von der Form zur Richtung

Growth cones, the terminal structures of elongating neurites are
important for development and regeneration. The second messenger
cAMP regulates both processes. cAMP is also known to induce growth
cone turning. By using time-lapse microscopy and release of cAMP
from biological inactive caged compounds the directional response
of neuronal growth cones was investigated. Intracellular gradients
were induced by asymmetric release of cAMP on one side of the
growth cone. Using a new method, which released the same amount
cAMP independent of the stimulation pattern it was possible to show
that pulsed release in contrast to continuous release was more
effective in inducing growth cone turning. From experiments with
several pharmacological agents it can be concluded that the protein
kinase A plays a major role for the cellular responses and that the
gradient steepness causes the different reactions. In cooperation
with other scientists it was ruled out that the different responses
were caused by non-linearities of the caged compound. Furthermore
cAMP gradients were visualized directly in HeLa cells expressing
cAMP sensitive ion channels as a reporter system. With this cell
line it was also possible to show that the stimulation pattern,
meaning pulsed and continuous release respectively, influences the
gradient shape. This finding was in accordance with published
theories and numerical calculations. Here it was shown for the
first time that the spatio-temporal properties of the intracellular
gradient are crucial for growth cone turning.