Neural Regeneration Research ›› 2015, Vol. 10 ›› Issue (9): 1388-1389.doi: 10.4103/1673-5374.165226

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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.

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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.