Functional analysis of Girdin family proteins in psyco-neurological disease and cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 26221304
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Nagoya University
• Principal Investigator: Takahashi Masahide 名古屋大学, 医学系研究科, 教授 (40183446)
• Co-Investigator(Kenkyū-buntansha): 榎本 篤 名古屋大学, 医学系研究科, 准教授 (20432255) ; 浅井 直也 名古屋大学, 医学部, 招へい教員 (80273233)
• Project Period (FY): 2014-05-30 – 2019-03-31
• Keywords: Girdin / Daple / 細胞運動 / 精神神経疾患 / がんの浸潤、転移 / 神経発生

Outline of Final Research Achievements

We studied the roles of the Akt substrate and actin-binding protein, Girdin and its family protein, Daple in the development of psyco-neurologic disorder and cancer. We found that Girdin is involved in the synapse formation of hippocampal neurons and their long-term potentiation. In addition, Girdin was shown to play an important role in cancer cell collective migration, and its phosphorylation in cancer-associated fibroblasts (CAF) is essential for CAF migration which leads to tumor progression.
We showed that Daple-deficient mice present hydrocephalus and their ependymal cilia lack coordinated orientation. Daple regulates microtubule dynamics at the anterior side of ependymal cells, which in turn orients the cilial basal bodies . These results demonstrate an important role for Daple in planar polarity in motile cilia. Moreover, we elucidated that Daple is involved in the activation of Wnt signaling, promoting invasion and metastasis of gastric cancer cells.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

細胞運動は発生過程における形態形成、生後の組織修復、免疫反応、血管新生、がんの浸潤・転移といった様々な生理的、病理的現象に重要な役割を果たしている。本研究においてわれわれが細胞運動に重要な機能を有する分子として発見したGirdinおよびDapleの精神神経疾患、がんの進展における役割とその分子機構を明らかにした。今後これらの知見をもとに疾患の新規治療法の開発に貢献する。