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Calcium/calmodulin-dependent protein kinase II regulates mammalian axon growth by affecting F-actin length in growth cone |
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| Authors: | Feng Xi Ren-Jie Xu Jin-Hui Xu Jin-Jin Ma Wei-Hua Wang Feng Wang Yan-Xia Ma Shi-Bin Qi Hong-Cheng Zhang Hao-Nan Zhang Xu-Zhen Qin Jian-Quan Chen Bin Li Chang-Mei Liu Hui-Lin Yang Bin Meng Saijilafu |
| Institution: | 1. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, Jiangsu, P. R. China
Feng Xi and Ren-Jie Xu contributed equally to this study.;2. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, Jiangsu, P. R. China Department of Orthopaedics, Suzhou Municipal Hospital, The Affiliated Hospital of Nanjing Medical University, Suzhou, Jiangsu, P. R. China Feng Xi and Ren-Jie Xu contributed equally to this study.;3. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, Jiangsu, P. R. China;4. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Science, Beijing, P. R. China Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China |
| Abstract: | While axon regeneration is a key determinant of functional recovery of the nervous system after injury, it is often poor in the mature nervous system. Influx of extracellular calcium (Ca2+) is one of the first phenomena that occur following axonal injury, and calcium/calmodulin-dependent protein kinase II (CaMKII), a target substrate for calcium ions, regulates the status of cytoskeletal proteins such as F-actin. Herein, we found that peripheral axotomy activates CaMKII in dorsal root ganglion (DRG) sensory neurons, and inhibition of CaMKII impairs axon outgrowth in both the peripheral and central nervous systems (PNS and CNS, respectively). Most importantly, we also found that the activation of CaMKII promotes PNS and CNS axon growth, and regulatory effects of CaMKII on axon growth occur via affecting the length of the F-actin. Thus, we believe our findings provide clear evidence that CaMKII is a critical modulator of mammalian axon regeneration. |
| Keywords: | axon growth CaMKII cytoskeleton F-actin sensory neurons |