論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	査読あり
表題	ARAP1 fine-tunes F-actin polymerization level in lymphocytes through RhoA inhibition.
掲載誌名	正式名：Frontiers in immunology 略　 称：Front Immunol ISSNコード：16643224/16643224
掲載区分	国外
巻・号・頁	16,pp.1591450
著者・共著者	Yoshihiro Ueda, Naoyuki Kondo, Yuji Kamioka, Tatsuo Kinashi
発行年月	2025/12
概要	Rho family of small GTPases play crucial roles in F-actin polymerization and actomyosin contractility, facilitating lymphocyte polarization, motility, and adhesion. However, the spatiotemporal cooperation of these processes remains unclear. In this study, we found that the dual GTPase-activating protein (GAP) ankyrin repeat and PH domain 1 (ARAP1) modulates RhoA activity through its Ras-association (RA) domain, which binds to Rac and Rap1 and is critical for F-actin polymerization and cell migration. ARAP1 was transiently recruited to cell protrusions following chemokine stimulation. ARAP1-deficient cells exhibited enhanced chemokine-directed migration, accompanied by increased RhoA activation and F-actin polymerization. Conversely, ARAP1 overexpression had the opposite effect and inhibited migration in a manner dependent on its RhoGAP domain. Notably, the RA domain bound Rap1 and Rac1 and was required for ARAP1-mediated RhoA inhibition. These findings indicate that ARAP1 modulates RhoA activity at Rac/Rap1-rich protrusions and fine-tunes F-actin polymerization and cell motility.
DOI	10.3389/fimmu.2025.1591450
PMID	41488654