Interleukin-6 promotes microtubule stability in axons via Stat3 protein–protein interactions

Autor: Lauren K. Wareham, Franklin D. Echevarria, Jennifer L. Sousa, Danielle O. Konlian, Gabrielle Dallas, Cathryn R. Formichella, Priya Sankaran, Peter J. Goralski, Jenna R. Gustafson, Rebecca M. Sappington
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: iScience, Vol 24, Iss 10, Pp 103141- (2021)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2021.103141
Popis: Summary: The interleukin-6 (IL-6) family of cytokines and its downstream effector, STAT3, are important mediators of neuronal health, repair, and disease throughout the CNS, including the visual system. Here, we elucidate a transcription-independent mechanism for the neuropoietic activities of IL-6 related to axon development, regeneration, and repair. We examined the outcome of IL-6 deficiency on structure and function of retinal ganglion cell (RGC) axons, which form the optic projection. We found that IL-6 deficiency substantially delays anterograde axon transport in vivo. The reduced rate of axon transport is accompanied by changes in morphology, structure, and post-translational modification of microtubules. In vivo and in vitro studies in mice and swine revealed that IL-6-dependent microtubule phenotypes arise from protein-protein interactions between STAT3 and stathmin. As in tumor cells and T cells, this STAT3-stathmin interaction stabilizes microtubules in RGCs. Thus, this IL-6-STAT3-dependent mechanism for axon architecture is likely a fundamental mechanism for microtubule stability systemically.
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