Affiliation:
1. Department of Cell Biology, Emory University School of Medicine,Atlanta, GA 30322, USA
Abstract
SUMMARY
During normal postnatal development, rat soleus (SOL) muscle fibers undergo a dramatic fast-to-slow myosin heavy chain (MyHC) isoform transformation. We exploited this phenomenon to evaluate the role of neurotrophin 4/5 (NT-4/5) in the regulation of muscle fiber phenotype. Intramuscular injections of recombinant NT-4/5 into the SOL muscle of rat neonates significantly accelerated the normal fast-to-slow MyHC isoform transformation. Sequestration of endogenous NT-4/5 with TrkB–IgG prevented this transformation from occurring. Administration of the other TrkB ligand, brain-derived neurotrophic factor (BDNF), did not affect the normal course of the MyHC isoform transformation in this muscle, indicating that the observed effect is NT-4/5 specific. Botulinum toxin blockade of synaptic transmission significantly disrupted the normal fast-to-slow MyHC isoform switch. Because administration of NT-4/5 to paralyzed muscles failed to restore the normal course of this MyHC transformation, we believe that the effect of NT-4/5 is not directly on the muscle fibers but that it probably activates or forms a type of retrograde signal to motoneurons. The developmental upregulation of NT-4/5 mRNA in rat SOL muscle fibers occurred earlier than the upregulation of MyHC I/b mRNA associated with muscle fiber transformation. This timing is consistent with the idea that NT-4/5 is involved in early events that lead to the upregulation of the slow MyHC isoform in this muscle.
Publisher
The Company of Biologists
Subject
Insect Science,Molecular Biology,Animal Science and Zoology,Aquatic Science,Physiology,Ecology, Evolution, Behavior and Systematics
Cited by
20 articles.
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