ETS Transcription Factor Erm Controls Subsynaptic Gene Expression in Skeletal Muscles
| Autor: | Roland M. Huber, Simon Hippenmeyer, David R. Ladle, Kenneth M. Murphy, Silvia Arber |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Transcriptional Activation
Neuroscience(all) Neuromuscular Junction Synaptic Membranes Down-Regulation DEVBIO Biology Receptors Nicotinic Synaptic Transmission Neuromuscular junction MOLNEURO Mice Myasthenia Gravis medicine Animals Muscle Skeletal Transcription factor Acetylcholine receptor Regulation of gene expression Cell Nucleus Mice Knockout Muscle Weakness Synapse assembly General Neuroscience ETS transcription factor family Receptor Aggregation Gene Expression Regulation Developmental Congenital myasthenic syndrome medicine.disease Cell biology DNA-Binding Proteins Cell nucleus medicine.anatomical_structure Mutation Cancer research Transcription Factors |
| Zdroj: | Neuron. 55(5):726-740 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2007.07.028 |
| Popis: | SummaryAccumulation of specific proteins at synaptic structures is essential for synapse assembly and function, but mechanisms regulating local protein enrichment remain poorly understood. At the neuromuscular junction (NMJ), subsynaptic nuclei underlie motor axon terminals within extrafusal muscle fibers and are transcriptionally distinct from neighboring nuclei. In this study, we show that expression of the ETS transcription factor Erm is highly concentrated at subsynaptic nuclei, and its mutation in mice leads to severe downregulation of many genes with normally enriched subsynaptic expression. Erm mutant mice display an expansion of the muscle central domain in which acetylcholine receptor (AChR) clusters accumulate, show gradual fragmentation of AChR clusters, and exhibit symptoms of muscle weakness mimicking congenital myasthenic syndrome (CMS). Together, our findings define Erm as an upstream regulator of a transcriptional program selective to subsynaptic nuclei at the NMJ and underscore the importance of transcriptional control of local synaptic protein accumulation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|