First Author | Wareham LK | Year | 2021 |
Journal | iScience | Volume | 24 |
Issue | 10 | Pages | 103141 |
PubMed ID | 34646984 | Mgi Jnum | J:313566 |
Mgi Id | MGI:6791284 | Doi | 10.1016/j.isci.2021.103141 |
Citation | Wareham LK, et al. (2021) Interleukin-6 promotes microtubule stability in axons via Stat3 protein-protein interactions. iScience 24(10):103141 |
abstractText | 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. |