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Molecular and Cellular Biology, October 2007, p. 7113-7124, Vol. 27, No. 20
0270-7306/07/$08.00+0     doi:10.1128/MCB.00928-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Reelin Signals through Phosphatidylinositol 3-Kinase and Akt To Control Cortical Development and through mTor To Regulate Dendritic Growth{triangledown}

Yves Jossin and André M. Goffinet*

Université Catholique de Louvain, Center for Neurosciences, Avenue E. Mounier, 73, DENE 7382, B1200 Brussels, Belgium

Received 25 May 2007/ Returned for modification 27 June 2007/ Accepted 28 July 2007

Reelin is an extracellular matrix protein with various functions during development and in the mature brain. It activates different signaling cascades in target cells, one of which is the phosphatidylinositol 3-kinase (PI3K) pathway, which we investigated further using pathway inhibitors and in vitro brain slice and neuronal cultures. We show that the mTor (mammalian target of rapamycin)-S6K1 (S6 kinase 1) pathway is activated by Reelin and that this depends on Dab1 (Disabled-1) phosphorylation and activation of PI3K and Akt (protein kinase B). PI3K and Akt are required for the effects of Reelin on the organization of the cortical plate, but their downstream partners mTor and glycogen synthase kinase 3ß (GSK3ß) are not. On the other hand, mTor, but not GSK3ß, mediates the effects of Reelin on the growth and branching of dendrites of hippocampal neurons. In addition, PI3K fosters radial migration of cortical neurons through the intermediate zone, an effect that is independent of Reelin and Akt.

* Corresponding author. Mailing address: Université Catholique de Louvain, Center for Neurosciences, Avenue E. Mounier, 73, DENE 7382, B1200 Brussels, Belgium. Phone: 32 2764 7386. Fax: 32 2765 7385. E-mail: andre.goffinet{at}uclouvain.be

{triangledown} Published ahead of print on 13 August 2007.

Molecular and Cellular Biology, October 2007, p. 7113-7124, Vol. 27, No. 20
0270-7306/07/$08.00+0     doi:10.1128/MCB.00928-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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