Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Wareham LK 

PROVIDER: S-EPMC8496173 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC6260213 | biostudies-literature
| S-EPMC3619811 | biostudies-other
| S-EPMC7275735 | biostudies-literature
| S-EPMC2717962 | biostudies-literature
| S-EPMC3469518 | biostudies-literature
| S-EPMC6602802 | biostudies-literature
| S-EPMC5576569 | biostudies-literature
| S-EPMC3504791 | biostudies-literature
| S-EPMC5064366 | biostudies-literature
| S-EPMC4911381 | biostudies-literature