title: Notch, epidermal growth factor receptor, and beta1-integrin pathways are coordinated in neural stem cells.
abstract: Notch1 and beta1-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 beta1-integrins are co-expressed and that these proteins cooperate with the epidermal growth factor receptor in neural progenitors. We describe data that suggests that beta1-integrins may affect Notch signaling through 1) physical interaction (sequestration) of the Notch intracellular domain fragment by the cytoplasmic tail of the beta1-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 beta1-integrin, Notch1, and tyrosine kinase receptor signaling pathways. We speculate that this will require the presence of the adequate beta1-activating extracellular matrix or growth factors in restricted regions of the central nervous system and namely in neurogenic niches.
authors.affiliation: INSERM U368, Biologie Moléculaire du Développement, Ecole Normale Supérieure, Paris, France. lsc@sanger.ac.uk
authors.forename: Lia Scotti
authors.initials: LS
authors.lastname: Campos
authors.forename: Laurence
authors.initials: L
authors.lastname: Decker
authors.forename: Verdon
authors.initials: V
authors.lastname: Taylor
authors.forename: William
authors.initials: W
authors.lastname: Skarnes
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D019012:Integrin beta1 / Q000378:metabolism*; D008345:Manganese / Q000737:chemistry; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D051880:Receptors, Notch / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors
chemical_list: D051242:Caveolin 1; D006133:Growth Substances; D019012:Integrin beta1; D051880:Receptors, Notch; D016222:Fibroblast Growth Factor 2; D008345:Manganese; D005982:Glutathione Transferase; D066246:ErbB Receptors