A Retrograde Neuronal Survival Response: Target-Derived Neurotrophins Regulate MEF2D and bcl-w
| Autor: | Heather M. Heerssen, Christoph Karch, Fiona L. Watson, Michael E. Greenberg, Tae Kyung Kim, Rosalind A. Segal, Stephanie L. Courchesne, Maria F. Pazyra-Murphy, Aymeric Hans, Katharina E. Cosker |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Mef2
Sensory Receptor Cells Cell Survival Green Fluorescent Proteins Nerve Tissue Proteins Stimulation Transfection Article Ganglia Spinal Chlorocebus aethiops In Situ Nick-End Labeling medicine Animals Nerve Growth Factors RNA Messenger Enzyme Inhibitors Cells Cultured Mitogen-Activated Protein Kinase 7 Regulation of gene expression biology General Neuroscience Embryo Mammalian Protein Tyrosine Phosphatases Non-Receptor Sensory neuron Rats Cell biology Nerve growth factor medicine.anatomical_structure Gene Expression Regulation Proto-Oncogene Proteins c-bcl-2 nervous system biology.protein RNA Interference Signal transduction Signal Transduction Neurotrophin |
| Zdroj: | The Journal of Neuroscience. 29:6700-6709 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | Survival and maturation of dorsal root ganglia sensory neurons during development depend on target-derived neurotrophins. These target-derived signals must be transmitted across long distances to alter gene expression. Here, we address the possibility that long-range retrograde signals initiated by target-derived neurotrophins activate a specialized transcriptional program. The transcription factor MEF2D is expressed in sensory neurons; we show that expression of this factor is induced in response to target-derived neurotrophins that stimulate the distal axons. We demonstrate that MEF2D regulates expression of an anti-apoptoticbcl-2family member,bcl-w. Expression ofmef2dandbcl-wis stimulated in response to activation of a Trk-dependent ERK5/MEF2 pathway, and our data indicate that this pathway promotes sensory neuron survival. We find thatmef2dandbcl-ware members of a larger set of retrograde response genes, which are preferentially induced by neurotrophin stimulation of distal axons. Thus, activation of an ERK5/MEF2D transcriptional program establishes and maintains the cellular constituents of functional sensory circuits. |
| Databáze: | OpenAIRE |
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