title: CD45-mediated fodrin cleavage during galectin-1 T cell death promotes phagocytic clearance of dying cells.
abstract: Disassembly and phagocytic removal of dying cells is critical to maintain immune homeostasis. The factors that regulate fragmentation and uptake of dying lymphocytes are not well understood. Degradation of fodrin, a cytoskeletal linker molecule that attaches CD45 to the actin cytoskeleton, has been described in apoptotic cells, although no specific initiator of fodrin degradation has been identified. CD45 is a glycoprotein receptor for galectin-1, an endogenous lectin that can trigger lymphocyte apoptosis, although CD45 is not required for phosphatidylserine externalization or DNA degradation during galectin-1 death. In this study, we show that fodrin degradation occurs during galectin-1 T cell death and that CD45 is essential for fodrin degradation to occur. In the absence of CD45, or if fodrin degradation is prevented, galectin-1-induced cell death is not accompanied by membrane blebbing, although phosphatidylserine externalization and DNA degradation proceed, indicating that fodrin degradation occurs via a distinct pathway compared with the pathway that leads to these other hallmarks of cell death. Moreover, there is slower phagocytic uptake by macrophages of T cells in which fodrin degradation is prevented, relative to T cells in which CD45-mediated fodrin degradation occurs. These studies identify a novel role for CD45 in regulating cellular disassembly and promoting phagocytic clearance during galectin-1-induced T cell death.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Mabel
authors.initials: M
authors.lastname: Pang
authors.forename: Jiale
authors.initials: J
authors.lastname: He
authors.forename: Pauline
authors.initials: P
authors.lastname: Johnson
authors.forename: Linda G
authors.initials: LG
authors.lastname: Baum
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D002352:Carrier Proteins / Q000378:metabolism*; D037483:Galectin 1 / Q000502:physiology*; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D008840:Microfilament Proteins / Q000378:metabolism*; D010587:Phagocytosis; D013601:T-Lymphocytes / Q000166:cytology*; D013049:Spectrin
chemical_list: D002352:Carrier Proteins; D037483:Galectin 1; D017493:Leukocyte Common Antigens; D008840:Microfilament Proteins; D013049:Spectrin