Pathogenesis of a neurodevelopmental disorder caused by human beta3 tubulin gene mutations

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430080
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Minoura Itsushi 国立研究開発法人理化学研究所, 脳科学総合研究センター, 客員研究員 (70373371)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: チューブリン / 外眼筋線維症 / 微小管 / ダイナミクス / キネシン / クライオ電子顕微鏡

Outline of Final Research Achievements

Mutation at R262 amino acid residue of human beta3 tubulin impairs axon growth which leads to congenital fibrosis of extraocular muscles type 3. A model of the axon growth defects was constructed, which was rescued by a mutation at L12 loop of KIF21A or of KIF5B. These mutations recover the binding of these kinesin molecules to microtubules composed of beta-3 tubulin. These kinesins may control the dynamics of beta-3-tubulin rich microtubules which play essential roles in neuronal development. Our result suggests that these kinesin control the dynamics of such microtubules and these microtubues are important for axon growth and steering during brain morphogenesis.

Free Research Field

生物物理学