Notch, epidermal growth factor receptor, and beta1-integrin pathways are coordinated in neural stem cells.
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.
Campos
Lia Scotti
LS
INSERM U368, Biologie Moléculaire du Développement, Ecole Normale Supérieure, Paris, France. lsc@sanger.ac.uk
Decker
Laurence
L
Taylor
Verdon
V
Skarnes
William
W
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
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