title: Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease.
abstract: Axonal maintenance, plasticity, and regeneration are influenced by signals from neighboring cells, in particular Schwann cells of the peripheral nervous system. Schwann cells produce neurotrophic factors, but the mechanisms by which ciliary neurotrophic factor (CNTF) and other neurotrophic molecules modify the axonal cytoskeleton are not well understood. In this paper, we show that activated signal transducer and activator of transcription-3 (STAT3), an intracellular mediator of the effects of CNTF and other neurotrophic cytokines, acts locally in axons of motoneurons to modify the tubulin cytoskeleton. Specifically, we show that activated STAT3 interacted with stathmin and inhibited its microtubule-destabilizing activity. Thus, ectopic CNTF-mediated activation of STAT3 restored axon elongation and maintenance in motoneurons from progressive motor neuronopathy mutant mice, a mouse model of motoneuron disease. This mechanism could also be relevant for other neurodegenerative diseases and provide a target for new therapies for axonal degeneration.
authors.affiliation: Institute for Clinical Neurobiology, University of Wuerzburg, 97078 Wuerzburg, Germany.
authors.forename: Bhuvaneish Thangaraj
authors.initials: BT
authors.lastname: Selvaraj
authors.forename: Nicolas
authors.initials: N
authors.lastname: Frank
authors.forename: Florian L P
authors.initials: FL
authors.lastname: Bender
authors.forename: Esther
authors.initials: E
authors.lastname: Asan
authors.forename: Michael
authors.initials: M
authors.lastname: Sendtner
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016472:Motor Neuron Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology; D009154:Mutation / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000502:physiology*; D050777:Stathmin / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D050777:Stathmin