中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (9): 1388-1389.doi: 10.4103/1673-5374.165226

• 观点:颅神经损伤修复保护与再生 • 上一篇    下一篇

微管蛋白折叠辅助因子在神经元形态发生和疾病中的作用

  

  • 收稿日期:2015-06-04 出版日期:2015-09-28 发布日期:2015-09-28

The roles of tubulin-folding cofactors in neuronal morphogenesis and disease

Misako Okumura, Masayuki Miura, Takahiro Chihara   

  1. Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan (Okumura M, Miura M, Chihara T)
    Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo, Japan (Miura M, Chihara T)
  • Received:2015-06-04 Online:2015-09-28 Published:2015-09-28
  • Contact: Takahiro Chihara, Ph.D., tchihara@mol.f.u-tokyo.ac.jp.
  • Supported by:

    This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology in Japan to MM and TC, the Japan Society for the Promotion of Science to MO, MM, and TC, and the Japan Science and Technology Agency to M.M. and TC.

摘要:

微管在神经元形态发生中有着重要作用,包括细胞分化,轴突生长和分支。微管是至少五个微管蛋白折叠辅助因子(TBCA-E),即一个多步骤过程形成的α-和β微管蛋白异源二聚体的聚合物。通过微管相关蛋白调节微管动力学对神经发育很重要。最近越来越多的证据表明,自由微管蛋白量的调控有助于调节微管动力学。微管蛋白折叠辅助因子是神经元形态发生的一个重要因素。虽然造成微管蛋白折叠辅助因子突变特异性人类疾病尚未确定,但人类DSCAM基因位于唐氏综合症的关键区域,并关联着唐氏综合征认知障碍。他们发现功能获得的表型唐氏综合症黏附分子的被抑制可造成微管蛋白折叠辅助因子减少。因此,微管蛋白折叠辅助因子可能有助于结构改动,功能改变,或者两者在唐氏综合症和其它神经病症中的神经电路重建。

Abstract:

Microtubules play important roles in neuronal morphogenesis, including cellular polarization, neurite growth, and branching. A microtubule is a polymer of α- and β-tubulin heterodimers that are formed by a multistep process assisted by at least five tubulin-folding cofactors (TBCA–E). Microtubule dynamics regulated by microtubule-associated proteins are important for neural development. Growing evidence suggests that regulation of the amount of free tubulins helps modulate microtubule dynamics. As have described here, TBCD is an essential factor for neuronal morphogenesis. Although specific human disorders caused by TBCD mutation have not been identified, human DSCAM is located in the Down syndrome critical region and is implicated in the cognitive disabilities seen in Down syndrome. We found that the gain-of-function phenotype of Dscam was suppressed by reduction in TBCD. Therefore, TBCD may contribute to structural alterations, functional alterations, or both of neural circuits in Down syndrome and other neurological disorders.