Fidgetin interacting with microtubule end binding protein EB3 affects axonal regrowth in spinal cord injury  

作　　者：Chao Ma Junpei Wang Qifeng Tu Weijuan Bo Zunlu Hu Run Zhuo Ronghua Wu Zhangji Dong Liang Qiang Yan Liu Mei Liu 

机构地区：[1]Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education,Co-innovation Center of Neuroregeneration,NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products,Nantong University,Nantong,Jiangsu Province,China [2]Medical School of Nantong University,Nantong,Jiangsu Province,China [3]Department of Neurobiology and Anatomy,Drexel University College of Medicine,Philadelphia,PA,USA

出　　处：《Neural Regeneration Research》2023年第12期2727-2732,共6页中国神经再生研究（英文版）

基　　金：the National Natural Science Foundation of China,Nos.32070725(to ML),82001295(to RHW),31970412(to YL);the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions。

摘　　要：Fidgetin,a microtubule-severing enzyme,regulates neurite outgrowth,axonal regeneration,and cell migration by trimming off the labile domain of microtubule polymers.Because maintenance of the microtubule labile domain is essential for axon initiation,elongation,and navigation,it is of interest to determine whether augmenting the microtubule labile domain via depletion of fidgetin serves as a therapeutic approach to promote axonal regrowth in spinal cord injury.In this study,we constructed rat models of spinal cord injury and sciatic nerve injury.Compared with spinal cord injury,we found that expression level of tyrosinated microtubules in the labile portion of microtubules continuously increased,whereas fidgetin decreased after peripheral nerve injury.Depletion of fidgetin enhanced axon regeneration after spinal cord injury,whereas expression level of end binding protein 3(EB3)markedly increased.Next,we performed RNA interference to knockdown EB3 or fidgetin.We found that deletion of EB3 did not change fidgetin expression.Conversely,deletion of fidgetin markedly increased expression of tyrosinated microtubules and EB3.Deletion of fidgetin increased the amount of EB3 at the end of neurites and thereby increased the level of tyrosinated microtubules.Finally,we deleted EB3 and overexpressed fidgetin.We found that fidgetin trimmed tyrosinated tubulins by interacting with EB3.When fidgetin was deleted,the labile portion of microtubules was elongated,and as a result the length of axons and number of axon branches were increased.These findings suggest that fidgetin can be used as a novel therapeutic target to promote axonal regeneration after spinal cord injury.Furthermore,they reveal an innovative mechanism by which fidgetin preferentially severs labile microtubules.

关 键 词：acetylated microtubules axon regeneration axonal branching axonal regrowth end binding protein 3 fidgetin microtubule dynamics sciatic nerve injury spinal cord injury tyrosinated microtubules 

分 类 号：R651.2[医药卫生—外科学]