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Papers In Press, published online ahead of print December 6, 2005
Wellcome Trust Sanger Institute, Wellcome Trust Sanger Institute, Cambridge CB10 1SA
Corresponding Author: lsc{at}sanger.ac.uk
Notch1 and ß1-integrins are cell surface receptors involved in the recognition of the niche that surrounds stem cells through cell-cell and cell-extra cellular matrix interactions, respectively. Notch1 is also involved in the control of cell fate choices in the developing central nervous system [1]. Here we report that Notch and ß1-integrins are co-expressed and that these proteins co-operate with the epidermal growth factor receptor in neural progenitors. We describe data that suggests that ß1-integrins may affect Notch signalling through 1) physical interaction (sequestration) of the Notch intra cellular domain fragment by the cytoplasmic tail of the ß1-integrin 2) by affecting trafficking of the Notch intra cellular domain via caveolin mediated mechanisms. Our findings suggest that caveolin1-containing lipid rafts play a role in the coordination and coupling of ß1-integrin, Notch1 and tyrosine kinase receptors signalling pathways. We speculate that this will require the presence of the adequate ß1-activating extra cellular matrix or growth factors in restricted regions of the central nervous system, and namely in neurogenic niches.
J. Biol. Chem, 10.1074/jbc.M511886200
Submitted on November 3, 2005
Revised on December 5, 2005
Accepted on December 6, 2005
Notch, EGFR and
1 integrin pathways are coordinated in neural stem cells
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