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NGF controls dendrite development in hippocampal neurons by binding to p75NTR and modulating the cellular targets of Notch

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Item Type:Article
Title:NGF controls dendrite development in hippocampal neurons by binding to p75NTR and modulating the cellular targets of Notch
Creators Name:Salama-Cohen, P. and Arevalo, M.A. and Meier, J. and Grantyn, R. and Rodríguez-Tebar, A.
Abstract:Notch and neurotrophins control neuronal shape, but it is not known whether their signaling pathways intersect. Here we report results from hippocampal neuronal cultures that are in support of this possibility. We found that low cell density or blockade of Notch signaling by a soluble Delta-Fc ligand decreased the mRNA levels of the nuclear targets of Notch, the homologues of enhancer-of-split 1 and 5 (Hes1/5). This effect was associated with enhanced sprouting of new dendrites or dendrite branches. In contrast, high cell density or exposure of low-density cultures to NGF increased the Hes1/5 mRNA, reduced the number of primary dendrites and promoted dendrite elongation. The NGF effects on both Hes1/5 expression and dendrite morphology were prevented by p75-antibody (a p75NTR-blocking antibody) or transfection with enhancer-of-split 6 (Hes6), a condition known to suppress Hes activity. Nuclear translocation of NF-kappaB was identified as a link between p75NTR and Hes1/5 because it was required for the up-regulation of these two genes. The convergence of the Notch and p75NTR signaling pathways at the level of Hes1/5 illuminates an unexpected mechanism through which a diffusible factor (NGF) could regulate dendrite growth when cell-cell interaction via Notch is not in action.
Keywords:Cell Nucleus Active Transport, Axons, Basic Helix-Loop-Helix Transcription Factors, Western Blotting, Cell Communication, Cell Nucleus, Cultured Cells, DNA-Binding Proteins, Dendrites, Hippocampus, Homeodomain Proteins, Computer-Assisted Image Processing, Ligands, Membrane Proteins, Biological Models, NF-kappa B, Nerve Growth Factor, Protein Binding, Messenger RNA, Nerve Growth Factor Receptors, Notch Receptors, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Animals, Mice
Source:Molecular Biology of the Cell
Publisher:American Society for Cell Biology
Page Range:339-347
Date:January 2005
Additional Information:Copyright (c) 2005 by The American Society for Cell Biology
Official Publication:https://doi.org/10.1091/mbc.E04-05-0438
PubMed:View item in PubMed

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