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Phagocytosis in macrophages is regulated by the ATP-binding cassette family gene ABCF1

Arora, H.; Choi, K. B.; Munro, L.; Pfeifer, C. G.; Jefferies, W. A.

2023-09-07 immunology
10.1101/2023.09.05.556419 bioRxiv
Show abstract

Phagocytosis is a conserved biological mechanism that is integral to tissue remodeling, clearance of apoptotic cells, and immune defense in animals. Additionally, it serves as a pivotal means of sustenance for diverse unicellular eukaryotes. In the context of mammals, this crucial role is fulfilled by specific cell types such as macrophages, monocytes, dendritic cells, and neutrophils. It is orchestrated by an array of receptors, kinases, cytoskeletal elements, and enzymes, working collaboratively to enable the recognition, engulfment, and internalization of particles. Despite its profound significance, the intricate mechanisms underpinning the regulation of this phenomenon remains enigmatic. In this study, we present compelling evidence indicating the involvement of ABCF1, a member of the ATP-binding cassette family, in the Fc{gamma}RIIA phagocytic pathway. ABCF1s contribution lies in facilitating downstream signal activation through interactions with Src family members and SYK, pivotal players in this cascade. Additionally, our findings highlight ABCF1s essentiality in the biosynthesis of various SFKs (Src family kinases) and MAPKs (mitogen-activated protein kinases). These molecules collectively oversee the orchestration of phagocytic cup formation, a pivotal step governing the engulfment process within macrophages. Consequently, the regulation of ABCF1 presents a potential avenue for modulating phagocytosis, allowing for the precise modulation of this fundamental process to either enhance or attenuate according to the specific physiological demands.

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