title: Anterograde axonal transport of glial cell line-derived neurotrophic factor and its receptors in rat hypoglossal nerve.
abstract: Glial cell line-derived neurotrophic factor is one of the most potent motoneuron survival factors yet identified. Although retrograde transport of trophic factors to the cell body is thought to be an important process in motoneuron survival, the transport pathways that lead to interaction of glial cell line-derived neurotrophic factor with its receptors is not known. We have used a double ligated hypoglossal nerve preparation to investigate transport of endogenous glial cell line-derived neurotrophic factor and its receptors, glial cell line-derived neurotrophic factor family receptor alpha1 and receptor re-arranged during transfection. Glial cell line-derived neurotrophic factor was found to accumulate at the distal ligature, indicating retrograde transport and consistent with its motoneuron survival effects. In addition, we observed accumulation of glial cell line-derived neurotrophic factor and its receptors at the proximal ligature, indicating anterograde transport. This finding is not predicted by neurotrophic theory. Staining for glial cell line-derived neurotrophic factor in the motor axons was punctate, suggesting involvement of transport vesicles. Results obtained using immunohistochemistry and reverse transcription-polymerase chain reaction provide evidence for the synthesis of glial cell line-derived neurotrophic factor and glial cell line-derived neurotrophic factor family receptor alpha1 in Schwann cells and glial cell line-derived neurotrophic factor family receptor alpha1 and receptor re-arranged during transfection in motoneuron cell bodies. When the motor axons were separated from the cell body by avulsion, glial cell line-derived neurotrophic factor remained in the vicinity of the Schwann cells and did not accumulate at the proximal ligature. Our results indicate anterograde transport of Schwann cell-derived glial cell line-derived neurotrophic factor, which is dependent on binding to its cell body-derived receptors. These findings suggest a mechanism for collection of glial cell line-derived neurotrophic factor from multiple Schwann cells which surround motor axons. We propose that in addition to its role in motoneuron survival, glial cell line-derived neurotrophic factor may also modulate local neuronal effects in distal regions of the nerve.
authors.affiliation: Department of Anatomy and Structural Biology, University of Otago, P. O. Box 913, Dunedin, New Zealand. fraser.russell@stonebow.otago.ac.nz
authors.forename: F D
authors.initials: FD
authors.lastname: Russell
authors.forename: K
authors.initials: K
authors.lastname: Koishi
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.forename: I S
authors.initials: IS
authors.lastname: McLennan
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D003964:Diaphragm / Q000166:cytology / Q000294:innervation / Q000378:metabolism; D029721:Drosophila Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D007002:Hypoglossal Nerve / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000294:innervation / Q000378:metabolism; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000166:cytology / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D014059:Tongue / Q000166:cytology / Q000294:innervation / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C495041:Gdnf protein, rat; C494989:Gfra1 protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila