PT  - JOURNAL ARTICLE
AU  - Patrick Essletzbichler
AU  - Vitaly Sedlyarov
AU  - Fabian Frommelt
AU  - Didier Soulat
AU  - Leonhard X Heinz
AU  - Adrijana Stefanovic
AU  - Benedikt Neumayer
AU  - Giulio Superti-Furga
TI  - A genome-wide CRISPR functional survey of the human phagocytosis molecular machinery
AID  - 10.26508/lsa.202201715
DP  - 2023 Apr 01
TA  - Life Science Alliance
PG  - e202201715
VI  - 6
IP  - 4
4099  - https://www.life-science-alliance.org/content/6/4/e202201715.short
4100  - https://www.life-science-alliance.org/content/6/4/e202201715.full
SO  - Life Sci. Alliance2023 Apr 01; 6
AB  - 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 importance, 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 identified 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 interpret genome-wide screens.