Explore of unconventional microtubules

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04047
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Osaka City University
• Principal Investigator: Hirotsune Shinji 大阪市立大学, 大学院医学研究科, 教授 (80337526)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 細胞骨格 / 神経発生 / 神経変性疾患 / 細胞内物質輸送

Outline of Final Research Achievements

We demonstrated that αSyn-bound tMTs carrying 14pfs, was confirmed by immuno-TEM analysis. This is the first evidence that shows the distinctive function of MTs with unconventional pfs numbers. Although in vitro tubulin polymerization yields MTs comprising 15pfs, the MTs in mammalian cells were previously thought to exclusively contain 13-pfs 6. MTs carrying 14pfs yield a helical arrangement 60 that is unsuitable for kinesin1 movement. However, tMTs would not be used for regular cytoskeletal MTs, as they are too small to provide a trafficking rail for motor proteins. Rather, tMTs are used as a transport platform to the periphery for proteins such as cytoplasmic dynein and the dynactin complex for which a helical pfs arrangement is not disadvantageous. It is worth exploring the distinctive functions of unconventional MTs through the identification of MAPs that can recognize MTs with unconventional pfs numbers.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

非定型微小管の進化と神経機能の高度化の研究は高度な神経機能をもつヒトの中枢神経研究に多大な示唆を与えることが期待される。さらに非定型微小管が神経の部位によってどのような特殊性を持っているのかの解析、たとえば運動神経と感覚神経でどのように異なっているのかの解明はALSの病態生理の解明に資することが期待される。さらに中枢神経系の部位特異的なパターンの解析はその領域での軸索伸展やネットワーク形成の制御の解明につながることが期待される一方、その機構の破綻は神経変性疾患や精神神経疾患の病態解明や新たな治療戦略の創出につながることが期待される。