O-GlcNAc glycosylation of p27(kip1) promotes astrocyte migration and functional recovery after spinal cord contusion.

Glial scar formation derived from astrocyte proliferation and migration influences the functional recovery after spinal cord injury. Cyclin-dependent kinase inhibitor p27(kip1), whose activity is closely related to its phosphorylation state, reportedly regulates astrocyte proliferation and migration. In this study, we reported that p27(Kip1) undergoes O-GlcNAc modification at Ser 2, Ser 110 and Thr 197. Inhibiting O-GlcNAcylation on Ser 2 by gene mutation (S2A) attenuated the phosphorylation of Ser 10, and vice versa. Interestingly, compared with wild type p27(Kip1), S2A p27(Kip1) displayed a decreased interaction with CRM1 and reduced nuclear export following serum starvation and release. In addition, the interaction between stathmin and S2A p27(Kip1) was also decreased. Cytoskeletal proteins microtubules appeared high density in astrocytes transfected with S2A p27(Kip1) especially at the leading edge of the scratch wound. Accordingly, scratch-wound assay revealed that the motility of astrocytes transfected with S2A p27(Kip1) was faster than that of control. Finally, we injected lentiviral vectors immediately after spinal cord contusion, and found the lesion volume of the rat injected with S2A p27(Kip1) was smaller than that of rat injected with wild type p27(Kip1). Besides, the BBB and CBS behavioral tests showed greater functional recovery in S2A p27(Kip1) treated rats. Taken together, our findings revealed a novel function of O-GlcNAc modification of p27(Kip1) in mediating astrocytes migration and functional recovery after spinal cord contusion.