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ARF1 recruits RAC1 to leading edge in neutrophil chemotaxis

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/67628

Title: ARF1 recruits RAC1 to leading edge in neutrophil chemotaxis
Authors: Mazaki, Yuichi Browse this author
Onodera, Yasuhito Browse this author →KAKEN DB
Higashi, Tsunehito Browse this author →KAKEN DB
Horinouchi, Takahiro Browse this author →KAKEN DB
Oikawa, Tsukasa Browse this author →KAKEN DB
Sabe, Hisataka Browse this author →KAKEN DB
Keywords: Chemotaxis
ARF1
GBF1
RAC1
Issue Date: 2-Oct-2017
Publisher: BioMed Central
Journal Title: Cell communication and signaling
Volume: 15
Start Page: 36
Publisher DOI: 10.1186/s12964-017-0193-y
Abstract: Background: The small GTPase ARF1 mediates membrane trafficking mostly from the Golgi, and is essential for the G protein-coupled receptor (GPCR)-mediated chemotaxis of neutrophils. In this process, ARF1 is activated by the guanine nucleotide exchanger GBF1, and is inactivated by the GTPase-activating protein GIT2. Neutrophils generate the Gβγ-PAK1-αPIX-GIT2 linear complex during GPCR-induced chemotaxis, in which αPIX activates RAC1/CDC42, which then employs PAK1. However, it has remained unclear as to why GIT2 is included in this complex. Results: We investigated the association between ARF1 and RAC1/CDC42 during the fMLP-stimulated chemotaxis of HL60 cells. We found that the silencing of GBF1 significantly impaired the recruitment of RAC1 to the leading edges, but not PAK1, αPIX, RAC2, or CDC42. A significant population of RAC1 colocalized with ARF1 at the leading edges in stimulated cells, whereas fMLP activated both ARF1 and ARF5. Consistently, the silencing of ARF1, but not ARF5, impaired the recruitment of RAC1, whereas the silencing of RAC1 did not affect the recruitment of ARF1 to the leading edges. Conclusions: Our results indicated that the activation of ARF1 triggers the plasma membrane recruitment of RAC1 in GPCR-mediated chemotaxis, which is essential for cortical actin remodeling. Thus, membrane remodeling at the leading edges appears to precede actin remodeling in chemotaxis. Together with the fact that GIT2, which inactivates ARF1, is an integral component of the machinery activating RAC1, we proposed a model in which the ARF1-RAC1 linkage enables the regulation of ARF1 by repetitive on/off cycles during GPCR-mediated neutrophil chemotaxis.
Rights: http://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/67628
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 真崎 雄一

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