O-GlcNAc glycosylation of p27(kip1) promotes astrocyte migration and functional recovery after spinal cord contusion.
O-GlcNAc glycosylation of p27(kip1) promotes astrocyte migration and functional recovery after spinal cord contusion.
复制标题
p27(kip1) 的 O-GlcNAc 糖基化促进脊髓挫伤后星形胶质细胞迁移和功能恢复。
DOI：
10.1016/j.yexcr.2015.11.007
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发表时间：
2015-12
影响因子：
3.7
通讯作者：
Shen Aiguo
中科院分区：
文献类型：
--
作者：
Mao Xingxing;Zhang Dongmei;Tao Tao;Liu Xiaojuan;Sun Xiaolei;Wang Youhua;Shen Aiguo
星形胶质细胞增殖和迁移形成的胶质瘢痕影响脊髓损伤后功能的恢复。细胞周期蛋白依赖性激酶抑制因子p27kip1的活性与其磷酸化状态密切相关，据报道，p27kip1调节星形胶质细胞的增殖和迁移。在本研究中，我们报道了p27Kip1在Ser2、Ser110和Thr197处经历了O-GlcNAc修饰。通过基因突变(S2A)抑制Ser2上的O-GlcN酰化可减弱Ser10的磷酸化，反之亦然。有趣的是，与野生型p27Kip1相比，S2Ap27Kip1在血清饥饿和释放后与CRM1的相互作用减少，核输出减少。此外，Stathmin与S2Ap27Kip1的相互作用也减弱。在转导S2Ap27Kip1基因的星形胶质细胞中，细胞骨架蛋白微管密度较高，尤其是在划痕前缘。划痕实验显示，转导S2Ap27Kip1的星形胶质细胞的运动速度明显快于对照组。最后，我们在脊髓挫伤后立即注射慢病毒载体，发现注射S2Ap27Kip1的大鼠的损伤体积小于注射野生型p27Kip1的大鼠。此外，BBB和CBS行为测试显示S2Ap27Kip1治疗组大鼠的功能恢复较好。综上所述，我们的研究结果揭示了p27Kip1的O-GlcNAc修饰在介导脊髓挫伤后星形胶质细胞迁移和功能恢复中的新功能。
Glial scar formation derived from astrocyte proliferation and migration influences the functional recovery after spinal cord injury. Cyclin-dependent kinase inhibitor p27kip1, whose activity is closely related to its phosphorylation state, reportedly regulates astrocyte proliferation and migration. In this study, we reported that p27Kip1undergoes 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 p27Kip1, S2A p27Kip1displayed a decreased interaction with CRM1 and reduced nuclear export following serum starvation and release. In addition, the interaction between stathmin and S2A p27Kip1was also decreased. Cytoskeletal proteins microtubules appeared high density in astrocytes transfected with S2A p27Kip1especially at the leading edge of the scratch wound. Accordingly, scratch-wound assay revealed that the motility of astrocytes transfected with S2A p27Kip1was 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 p27Kip1was smaller than that of rat injected with wild type p27Kip1. Besides, the BBB and CBS behavioral tests showed greater functional recovery in S2A p27Kip1treated rats. Taken together, our findings revealed a novel function of O-GlcNAc modification of p27Kip1in mediating astrocytes migration and functional recovery after spinal cord contusion.
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影响因子：
64.5
作者：
Etienne-Manneville, S;Hall, A
通讯作者：
Hall, A
影响因子：
5.3
作者：
GALE, K;KERASIDIS, H;WRATHALL, JR
通讯作者：
WRATHALL, JR
影响因子：
16.6
作者：
Hart GW;Slawson C;Ramirez-Correa G;Lagerlof O
通讯作者：
Lagerlof O
影响因子：
50.3
作者：
Baldassarre, G;Belletti, B;Colombatti, A
通讯作者：
Colombatti, A
DOI：
10.1074/jbc.a114.100762
发表时间：
2015-03
期刊：
The Journal of Biological Chemistry
影响因子：
--
作者：
N. Ishida;Taichi Hara;T. Kamura;Minoru Yoshida;K. Nakayama;K. Nakayama
通讯作者：
N. Ishida;Taichi Hara;T. Kamura;Minoru Yoshida;K. Nakayama;K. Nakayama