A genome-wide CRISPR functional survey of the human phagocytosis molecular machinery
Essletzbichler P, Sedlyarov V, Frommelt F, Soulat D, Heinz LX, Stefanovic A, Neumayer B, Superti-Furga G (2023)
Publication Type: Journal article
Publication year: 2023
Journal
Book Volume: 6
Journal Issue: 4
Abstract
Phagocytosis, the process by which cells engulf large particles, plays a vital role in driving tissue clearance and host defense. Its dysregulation is connected to autoimmunity, toxic accumulation of proteins, and increased risks for infections. Despite its im-portance, we lack full understanding of all molecular components involved in the process. To create a functional map in human cells, we performed a genome-wide CRISPRko FACS screen that identified 716 genes. Mapping those hits to a comprehensive protein-protein interaction network annotated for functional cellular processes allowed retrieval of protein complexes iden-tified multiple times and detection of missing phagocytosis regulators. In addition to known components, such as the Arp2/3 complex, the vacuolar-ATPase-Rag machinery, and the Wave-2 complex, we identified and validated new phagocytosis-relevant functions, including the oligosaccharyltransferase complex (MAGT1/SLC58A1, DDOST, STT3B, and RPN2) and the hypusine pathway (eIF5A, DHPS, and DOHH). Overall, our phagocytosis network comprises elements of cargo uptake, shuffling, and biotransformation through the cell, providing a resource for the identification of potential novel drivers for diseases of the endo-lysosomal system. Our approach of integrating protein-protein interaction offers a broadly applicable way to functionally in-terpret genome-wide screens.
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APA:
Essletzbichler, P., Sedlyarov, V., Frommelt, F., Soulat, D., Heinz, L.X., Stefanovic, A.,... Superti-Furga, G. (2023). A genome-wide CRISPR functional survey of the human phagocytosis molecular machinery. Life Science Alliance, 6(4). https://dx.doi.org/10.26508/lsa.202201715
MLA:
Essletzbichler, Patrick, et al. "A genome-wide CRISPR functional survey of the human phagocytosis molecular machinery." Life Science Alliance 6.4 (2023).
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