Multifunctional role of the ubiquitin proteasome pathway in phagocytosis

• Published in: Progress in molecular biology and translational science Vol. 194; pp. 179 - 217
• Main Authors: Lalnunthangi, Angela, Dakpa, Gyaltsen, Tiwari, Swati
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 2023
• Subjects: Complement receptor; Endocytosis; Fc receptor; Humans; Innate immunity; MVB; Phagocyte; Phagocytes - metabolism; Phagocytosis; Phagosome; Proteasome; Proteasome Endopeptidase Complex - metabolism; Signaling; Ubiquitin; Ubiquitin - metabolism; Ubiquitin; Complement receptor; Signaling; Fc receptor; MVB; Innate immunity; Phagosome; Phagocytosis; Phagocyte; Proteasome
• DOI: 10.1016/bs.pmbts.2022.06.023
• ISSN: 1877-1173; 1878-0814

Phagocytosis is a specialized form of endocytosis where large cells and particles (>0.5μm) are engulfed by the phagocytic cells, and ultimately digested in the phagolysosomes. This process not only eliminates unwanted particles and pathogens from the extracellular sources, but also eliminates apoptotic cells within the body, and is critical for maintenance of tissue homeostasis. It is believed that both endocytosis and phagocytosis share common pathways after particle internalization, but specialized features and differences between these two routes of internalization are also likely. The recruitment and removal of each protein/particle during the maturation of endocytic/phagocytic vesicles has to be tightly regulated to ensure their timely action. Ubiquitin proteasome pathway (UPP), degrades unwanted proteins by post-translational modification of proteins with chains of conserved protein Ubiquitin (Ub), with subsequent recognition of Ub chains by the 26S proteasomes and substrate degradation by this protease. This pathway utilizes different Ub linkages to modify proteins to regulate protein–protein interaction, localization, and activity. Due to its vast number of targets, it is involved in many cellular pathways, including phagocytosis. This chapters describes the basic steps and signaling in phagocytosis and different roles that UPP plays at multiple steps in regulating phagocytosis directly, or through its interaction with other phagosomal proteins. How aberrations in UPP function affect phagocytosis and their association with human diseases, and how pathogens exploit this pathway for their own benefit is also discussed.