RT Journal Article SR Electronic T1 Posttranslational Modification of Sox11 Regulates RGC Survival and Axon Regeneration JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0358-20.2020 DO 10.1523/ENEURO.0358-20.2020 VO 8 IS 1 A1 Kun-Che Chang A1 Minjuan Bian A1 Xin Xia A1 Ankush Madaan A1 Catalina Sun A1 Qizhao Wang A1 Liang Li A1 Michael Nahmou A1 Takahiko Noro A1 Satoshi Yokota A1 Joana Galvao A1 Alexander Kreymerman A1 Bogdan Tanasa A1 Yang Hu A1 Jeffrey L. Goldberg YR 2021 UL http://www.eneuro.org/content/8/1/ENEURO.0358-20.2020.abstract AB The failure of adult CNS neurons to survive and regenerate their axons after injury or in neurodegenerative disease remains a major target for basic and clinical neuroscience. Recent data demonstrated in the adult mouse that exogenous expression of Sry-related high-mobility-box 11 (Sox11) promotes optic nerve regeneration after optic nerve injury but exacerbates the death of a subset of retinal ganglion cells (RGCs), α-RGCs. During development, Sox11 is required for RGC differentiation from retinal progenitor cells (RPCs), and we found that mutation of a single residue to prevent SUMOylation at lysine 91 (K91) increased Sox11 nuclear localization and RGC differentiation in vitro. Here, we explored whether this Sox11 manipulation similarly has stronger effects on RGC survival and optic nerve regeneration. In vitro, we found that non-SUMOylatable Sox11K91A leads to RGC death and suppresses axon outgrowth in primary neurons. We furthermore found that Sox11K91A more strongly promotes axon regeneration but also increases RGC death after optic nerve injury in vivo in the adult mouse. RNA sequence (RNA-seq) data showed that Sox11 and Sox11K91A increase the expression of key signaling pathway genes associated with axon growth and regeneration but downregulated Spp1 and Opn4 expression in RGC cultures, consistent with negatively regulating the survival of α-RGCs and ipRGCs. Thus, Sox11 and its SUMOylation site at K91 regulate gene expression, survival and axon growth in RGCs, and may be explored further as potential regenerative therapies for optic neuropathy.