RT Journal Article
SR Electronic
T1 Reelin Signals through Apolipoprotein E Receptor 2 and Cdc42 to Increase Growth Cone Motility and Filopodia Formation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 14759
OP 14772
DO 10.1523/JNEUROSCI.4036-10.2010
VO 30
IS 44
A1 Leemhuis, Jost
A1 Bouché, Elisabeth
A1 Frotscher, Michael
A1 Henle, Frank
A1 Hein, Lutz
A1 Herz, Joachim
A1 Meyer, Dieter K.
A1 Pichler, Marina
A1 Roth, Günter
A1 Schwan, Carsten
A1 Bock, Hans H.
YR 2010
UL http://www.jneurosci.org/content/30/44/14759.abstract
AB Lipoprotein receptor signaling regulates the positioning and differentiation of postmitotic neurons during development and modulates neuronal plasticity in the mature brain. Depending on the contextual situation, the lipoprotein receptor ligand Reelin can have opposing effects on cortical neurons. We show that Reelin increases growth cone motility and filopodia formation, and identify the underlying signaling cascade. Reelin activates the Rho GTPase Cdc42, known for its role in neuronal morphogenesis and directed migration, in an apolipoprotein E receptor 2-, Disabled-1-, and phosphatidylinositol 3-kinase-dependent manner. We demonstrate that neuronal vesicle trafficking, a Cdc42-controlled process, is increased after Reelin treatment and further provide evidence that the peptidergic VIP/PACAP38 system and Reelin can functionally interact to promote axonal branching. In conclusion, Reelin-induced activation of Cdc42 contributes to the regulation of the cytoskeleton of individual responsive neurons and converges with other signaling cascades to orchestrate Rho GTPase activity and promote neuronal development. Our data link the observation that defects in Rho GTPases and Reelin signaling are responsible for developmental defects leading to neurological and psychiatric disorders.