Receptor tyrosine kinases and respiratory motor plasticity.
Protein kinases are a family of enzymes that transfer a phosphate group from adenosine tri-phosphate to an amino acid residue on a protein. The receptor tyrosine kinases (RTKs) are expressed on the outer cell membrane, bind extracellular protein ligands, and phosphorylate tyrosine residues on other proteins-essentially permitting communication between cells. Such activity regulates multiple aspects of cellular physiology including cell growth and differentiation, adhesion, motility, cell death, and morphological and synaptic plasticity. This review will focus on the role of RTKs in respiratory motor plasticity, with particular emphasis on long-term changes in respiratory motoneuron function. Reflecting the predominant literature, specific attention will be devoted to the role of tropomyosin-related kinase type B (TrkB) activation on phrenic motoneuron activity. However, many RTKs share similar patterns of expression and mechanisms of ligand-induced activation and downstream signaling. Thus, a perspective based on TrkB-induced phrenic motor plasticity may provide insight into the potential roles of other RTKs in the neural control of breathing. Finally, understanding how different RTKs affect respiratory motor output in the long-term may provide future avenues for pharmacological development with the goal of increasing respiratory motor output in disorders such as obstructive sleep apnea and after spinal cord injury. This is best illustrated in recent studies where we have used small, highly diffusible molecules to transactivate TrkB receptors near phrenic motoneurons to improve breathing after cervical spinal cord injury.
Golder
Francis J
FJ
Department of Clinical Studies, University of Pennsylvania, Philadelphia, USA. golderf@vet.upenn.edu
D000818:Animals; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D012137:Respiratory System / Q000166:cytology* / Q000378:metabolism*
D020794:Receptor Protein-Tyrosine Kinases