title: Co-receptors are dispensable for tethering receptor-mediated phagocytosis of apoptotic cells.
abstract: During efferocytosis, phagocytic cells recognize dying cells by receptors binding to ligands specifically exposed on apoptotic cells. Multiple phagocytic receptors and some of their signaling pathways have been identified. However, the downstream pathways of tethering receptors that secure apoptotic cells remain elusive. It is generally assumed that tethering receptors induce signaling to mediate engulfment via interacting with co-receptors or other engulfment receptors located nearby. However, it is poorly understood whether co-receptors for tethering receptors exist during efferocytosis, and, if they do, whether they are indispensable for this process. Here, we address this issue using glycophosphatidylinositol (GPI)-anchored annexin A5 (Anxa5-GPI), an artificial tethering receptor without a putative co-receptor. Phagocytes expressing Anxa5-GPI exhibited enhanced binding of apoptotic cells, resulting in promoted ingestion of apoptotic cells in a phosphatidylserine-dependent manner. Anxa5-GPI-induced phagocytosis of apoptotic cells relied on the known cytoskeletal engulfment machinery but partially depended on the Elmo-Dock-Rac module or the integrin pathway. In addition, Anxa5-GPI-mediated efferocytosis provoked anti-inflammatory responses. Taken together, our work suggests that co-receptors are dispensable for tethering receptor-induced efferocytosis and that tethering receptors mediate the engulfment of apoptotic cells through multiple engulfment signaling pathways.
authors.affiliation: 1] School of Life Sciences and Bio Imaging Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea [2] Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: B
authors.initials: B
authors.lastname: Park
authors.affiliation: 1] School of Life Sciences and Bio Imaging Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea [2] Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.affiliation: 1] School of Life Sciences and Bio Imaging Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea [2] Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Moon
authors.affiliation: School of Life Sciences and Bio Imaging Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.
authors.forename: G
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: D-H
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Biology Education, College of Education, Chosun University, Gwangju 501-759, Korea.
authors.forename: J Hoon
authors.initials: JH
authors.lastname: Cho
authors.affiliation: 1] School of Life Sciences and Bio Imaging Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea [2] Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: D
authors.initials: D
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D057809:HEK293 Cells; D006801:Humans; D010586:Phagocytes / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology / Q000502:physiology*; D010718:Phosphatidylserines / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017304:Annexin A5; D010718:Phosphatidylserines; D011971:Receptors, Immunologic; C028495:phagocytosis receptor