Correlative Structural Analysis of Microtubule Dynamics Regulation by CRMP2

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08168
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Kobe University (2017); Institute of Physical and Chemical Research (2015-2016)
• Principal Investigator: Nitta Ryo 神戸大学, 医学研究科, 教授 (40345038)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 微小管 / CRMP2 / Kinesin / 軸索誘導 / 軸索反発 / X線結晶構造解析 / X線小角散乱 / クライオ電子顕微鏡

Outline of Final Research Achievements

The aim of this project is to elucidate the molecular and structural mechanisms of CRMP2-regulated axon induction/repulsion. During the neuronal cell development, CRMP2 localizes the tips of the future axon in which CRMP2 forms the hetero-trimer with GTP-tubulin to add tubulins to the plus-ends of microtubules. This effectively induces the axonal microtubule formation, and thus the axon is effectively elongated. On the other hand, phosphorylation of CRMP2 decreases the affinity between CRMP2 and microtubule. It is driven by the small conformational changes at the C-terminal tail of CRMP2 with shifting the surface charges, which not only alter the interactions within the CRMP2 tetramer but also alter the interactions with GTP-tubulin. Consequently, phosphorylated CRMP2 fails to form a hetero-trimer with GTP-tubulin, thus losing the ability to establish and maintain the axonal microtubules.

Free Research Field

構造生物学・細胞生物学