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J. Biol. Chem., Vol. 281, Issue 8, 5300-5309, February 24, 2006

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Notch, Epidermal Growth Factor Receptor, and 1-Integrin Pathways Are Coordinated in Neural Stem Cells^*

Lia Scotti Campos¹, Laurence Decker, Verdon Taylor^¶, and William Skarnes

From the INSERM U368, Biologie Moléculaire du Développement, Ecole Normale Supérieure, Paris, France, the ^¶Department of Molecular Embryology, Max Planck Institute of Immunobiology, Freiburg, Germany, and the Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom

Notch1 and 1-integrins are cell surface receptors involved in the recognition of the niche that surrounds stem cells through cell-cell and cell-extracellular matrix interactions, respectively. Notch1 is also involved in the control of cell fate choices in the developing central nervous system (Lewis, J. (1998) Semin. Cell Dev. Biol. 9, 583-589). Here we report that Notch and 1-integrins are co-expressed and that these proteins cooperate with the epidermal growth factor receptor in neural progenitors. We describe data that suggests that 1-integrins may affect Notch signaling through 1) physical interaction (sequestration) of the Notch intracellular domain fragment by the cytoplasmic tail of the 1-integrin and 2) affecting trafficking of the Notch intracellular domain via caveolin-mediated mechanisms. Our findings suggest that caveolin 1-containing lipid rafts play a role in the coordination and coupling of 1-integrin, Notch1, and tyrosine kinase receptor signaling pathways. We speculate that this will require the presence of the adequate 1-activating extracellular matrix or growth factors in restricted regions of the central nervous system and namely in neurogenic niches.

Received for publication, November 3, 2005 , and in revised form, December 5, 2005.

^* This study was supported by the Wellcome Trust and by the European Community Grant QLG3-CT-2000-00911. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by a Sanger Institute Postdoctoral Fellowship. To whom correspondence should be addressed. E-mail: lsc{at}sanger.ac.uk.

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