Aug 11, 2004

Neuregulin induces the expression of transcription factors and myosin heavy chains typical of muscle spindles in cultured human muscle

Proceedings of the National Academy of Sciences of the United States of America
Christian JacobsonG D Fischbach

Abstract

Neuregulin (NRG) (also known as ARIA, GGF, and other names) is a heparin sulfate proteoglycan secreted into the neuromuscular junction by innervating motor and sensory neurons. An integral part of synapse formation, we have analyzed NRG-induced changes in gene expression over 48 h in primary human myotubes. We show that in addition to increasing the expression of acetylcholine receptors on the myotube surface, NRG treatment results in a transient increase of several members of the early growth response (Egr) family of transcription factors. Three Egrs, Egr1, -2, and -3, are induced within the first hour of NRG treatment, with Egr1 and -3 RNA levels showing the most significant increases of approximately 9- and 16-fold, respectively. Also noted was a corresponding increase in protein levels for both of these transcription factors. Previous literature indicates that Egr3 expression is required for the formation of muscle spindle fibers, sensory organs that are distinct from skeletal muscle contractile fibers. At the molecular level, muscle spindle fibers express a unique subset of myosin heavy chains. Two isoforms of the myosin heavy chain, the slow development and neonatal, were found to be increased in our myotube cultures afte...Continue Reading

  • References54
  • Citations34

Mentioned in this Paper

Early Growth Response Protein 2
Spindle
EGR1 gene
EGR3 gene
Immediate-Early Proteins
Proteins, Recombinant DNA
NRG1 wt Allele
Neuregulins
Cholinergic Receptors
Gene Expression

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