PTEN-GSK3-MOB1 axis controls neurite outgrowth in vitro and in vivo

Mps One binder 1 (MOB1) is a core component of NDR/LATS kinase and a positive regulator of the Hippo signaling pathway. However, its role in neurite outgrowth still remains to be clarified. Here, we confirmed, for the first time, that MOB1 promoted neurite outgrowth and was involved in functional recovery after spinal cord injury (SCI) in mice. Mechanistically, we found that MOB1 stability was regulated by the PTEN-GSK3 axis. The MOB1 protein was significantly up-regulated in PTEN-knockdown neuronal cells. This effect was dependent on the lipid phosphatase activity of PTEN. Moreover, MOB1 was found to be a novel substrate for GSK3 that is phosphorylated on serine 146 and degraded via the ubiquitin-proteasome system (UPS). Finally, in vivo lentiviral-mediated silencing of PTEN promoted neurite outgrowth and functional recovery after SCI and this effect was reversed by down-regulation of MOB1. Taken together, this study provided mechanistic insight into how MOB1 acts as a novel and a necessary regulator in PTEN-GSK3 axis that controls neurite outgrowth after SCI.