ORIGINAL RESEARCH article
Front. Immunol.
Sec. B Cell Biology
ARAP1 fine-tunes F-actin polymerization level in lymphocytes through RhoA inhibition
Provisionally accepted
- Kansai Medical University, Hirakata, Japan
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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.
Keywords: chemokine, RhoA, RhoGAP, RA-domain, ARAP1, F-actin polymerization
Received: 11 Mar 2025; Accepted: 02 Dec 2025.
Copyright: © 2025 Ueda, Kondo, Kamioka and Kinashi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yoshihiro Ueda
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