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

iScience

Danielle O. Konlian¹  Peter J. Goralski¹  Jennifer L. Sousa¹  Jenna R. Gustafson¹  Rebecca M. Sappington¹  Franklin D. Echevarria²  Gabrielle Dallas³  Lauren K. Wareham³  Cathryn R. Formichella³  Priya Sankaran³ 

[1] Department of Neurobiology and Anatomy, Wake Forest School of Medicine, Atrium Health Wake Forest Baptist Medical Center, 1 Medical Center Boulevard, Winston-Salem, NC 27157, USA;Neuroscience Graduate Program, Vanderbilt University, Nashville, TN 37232, USA;Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA;

关键词: Immunology;    Molecular neuroscience;    Cellular neuroscience;    Cell biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown