期刊
ISCIENCE
卷 24, 期 10, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2021.103141
关键词
-
资金
- National Eye Institute [RO1EY020496, P30EY08126]
- Research to Prevent Blindness, Inc.
IL-6 deficiency delays anterograde axon transport in RGCs, leading to changes in microtubule morphology, structure, and post-translational modification. This is mediated by the protein-protein interaction between STAT3 and stathmin, which stabilizes microtubules in RGCs. It suggests a fundamental mechanism for microtubule stability systemically.
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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