Neuron
Volume 55, Issue 5, 6 September 2007, Pages 726-740
Journal home page for Neuron

Article
ETS Transcription Factor Erm Controls Subsynaptic Gene Expression in Skeletal Muscles

https://doi.org/10.1016/j.neuron.2007.07.028Get rights and content
Under an Elsevier user license
open archive

Summary

Accumulation 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.

MOLNEURO
DEVBIO

Cited by (0)

4

These authors contributed equally to this work.

5

Present address: Howard Hughes Medical Institute, Department of Biological Sciences, 385 Serra Mall, Stanford University, Stanford, CA 94305, USA.