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Mol. Cell. Biol. doi:10.1128/MCB.00928-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Reelin signals through PI3K and Akt to control cortical development, and through mTor to regulate dendritic growth

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

^* To whom correspondence should be addressed. Email: andre.goffinet{at}uclouvain.be.

	Abstract

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 PI3K (phosphatidylinositol 3-kinase) pathway that 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 (PKB, 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 GSK3 (Glycogen Synthase Kinase-3 beta) are not. On the other hand, mTor - but not GSK3 - 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.

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